Me planteo el hecho de que la Medicina, Salud o Higiene Escolar ha existido desde hace mucho tiempo, y que las interrelaciones entre la Salud y la Educación han tenido unos lazos de unión muy fuertes. A lo largo de todo este trabajo se puede perfectamente corroborar, ya que desde la época romana, árabe, etc. hasta nuestros días, existen datos a tener en cuenta y presente cuando tengamos que analizar la Medicina, Salud o Higiene Escolar. Destacar cómo el estilo de vida de la población y el medio ambiente, son las dos grandes causas que explican la mayoría de los problemas de salud del mundo desarrollado, así como que las acciones de Salud pasan por la prevención de enfermedad y la promoción de la Salud. Pues bien, dentro de esta última destaco la importancia de instaurar políticas alternativas de promoción de la salud ya desde la escuela, para modificar las actitudes y comportamiento de la población. Sin olvidar la participación y el diálogo con el profesor, elementos básicos en el aprendizaje de la salud. Por otra parte, la situación particular del Homo Sapiens en relación con sus problemas de salud/enfermedad viene especialmente configurada por su naturaleza sociocultural, la cual le capacita para transformar su medio, para transformarse a sí mismo y para desarrollar nuevos comportamientos. En el ejercicio de esta capacidad adquiere una importancia esencial el proceso educativo. Teniendo en cuenta lo anterior, en la reforma educativa y en sus aspectos curriculares aparece la salud y sus contenidos desarrollados. Salud que la debemos entender como un valor a cultivar en la escuela, que permita una vida sana y una población bien formada y más equilibrada. Se constata que el marco teórico de la Medicina Escolar española es desolador y mísero, viene reflejado por innumerables autores y escritores de la época, y así por un lado, la escuela que existe a principios del siglo XIX "no sirve para nada", "aparte que son pocas". "Las escuelas de la mayor parte de los pueblos españoles son locales sin luz y sin ventilación, donde los niños pierden en su desarrollo físico lo que pueden ganar en su desarrollo intelectual". Azorín publicó en 1908 "Los hijos de España" en donde se expresaba así: "En esta España no hay escuelas, los niños no pueden aprender a leer y escribir. Las escuelas que existen son antihigiénicas y lóbregas". Las conclusiones que se sacan del panorama educativo español durante el siglo XIX no pueden ser más claras: En primer lugar, sólo una minoría de niños tuvo acceso a la enseñanza, de entre estos, únicamente los mejor dotados económicamente pudieron hacer algún ejercicio físico, aunque de un marcado carácter militarista. En segundo lugar, destaca la ausencia de niñas en todos los aspectos higiénicos. En tercer lugar, la alimentación era pobre y la higiene escasa, y, por último, las materias de enseñanza inapropiadas. Vista la precaria situación de la escuela española así como la de la pedagogía sanitaria existente y paradójicamente, en comparación con otras actividades, España se ha caracterizado por su temprana capacidad para detectar la problemática sanitaria escolar en relación con otros países europeos. Así, las primeras normas oficiales de que tengamos noticia en España referidas a la Sanidad Escolar, datan de hace más de dos siglos, hacia 1770, y están incluidas en la Novísima Recopilación de las Leyes de España, Libro VII, Título Primero: "De las escuelas y maestros de primeras letras y de educación de niños". Sin embargo, las normas legales sobre Medicina, Sanidad e Higiene Escolar, consideradas en el conjunto de la legislación acerca de la enseñanza, extremadamente rica en toda clase de disposiciones, decretos, órdenes, regulaciones, etc., es más bien pobre y sobre todo teórica. Importante fue la creación en 1911 de la Inspección médico-escolar del Estado, por el doctor Tolosa Latour. Tuvo su refrendo legal en el real decreto de 16 de Junio de 1911, a través del Ministerio de Instrucción Pública y Bellas Artes. En el año 1975 aparece el Reglamento Provisional de Sanidad Escolar y en el año 1978, el decreto sobre Ordenación de los Servicios de Medicina e Higiene Escolar. Declarado nulo y sin ningún valor por el Tribunal Supremo, en una sentencia dictada el día 1 de diciembre de 1982. Ahora bien, todo esto sufre un cambio bastante brusco, pues hemos de tener en cuenta la aparición de las distintas Comunidades Autónomas, con la transferencia de competencias que ello conlleva. Así cada Autonomía tiene sus decretos, órdenes, leyes sobre Salud Escolar. De todas las Autonomías, decir que hay leyes sobre Salud Escolar en Aragón, Principado de Asturias, Extremadura, Galicia, Gobierno Vasco y en La Rioja. En las restantes Comunidades existen órdenes, decretos e incluso las actividades de Salud Escolar son incluidas en programas de Atención Primaria de Salud. En referencia a la Sanidad, Medicina e Higiene Escolar desarrollada en otros países, destaca la figura de Bernardo Ramazzini da Caspi, promotor de los orígenes de la medicina social. Johan Peter Frank, considerado como el fundador de la higiene pública, pasando por Jean Jacques Rousseau, que debemos erigir como el auténtico origen de la Medicina Escolar. En Europa, comenzamos con Inglaterra donde se cuida bastante a la Salud, Medicina o Higiene de los escolares. Se crea el Servicio de Sanidad Escolar de Inglaterra en 1974. La educación para la salud se considera parte del plan de estudio escolar. Algo parecido ocurre en Francia, donde el control médico de los escolares fue planteado sin duda por primera vez en el mundo, durante la Revolución Francesa de 1789. Italia posee unos Servicios de Salud Escolar municipales, en donde el médico escolar trabaja en un equipo multidisciplinar. En Holanda son los municipios o grupos de municipios que están asociados, los obligados por ley a tener un Servicio municipal de salud escolar. En la República Federal de Alemania, la salud escolar y la educación para la salud son objetivos principales del Servicio de Salud Pública (S.S.P.). Su financiación proviene principalmente del municipio (Gemeindem) y del estado (Laender). Bélgica tiene un programa para el control médico y psicológico de la población escolar, llevado a cabo por el Ministerio de Educación. En Dinamarca, son los municipios los responsables del examen médico de todos los preescolares y escolares. El médico escolar y la enfermera participan junto con los maestros en la educación para la salud escolar. En Luxemburgo, el Ministerio de Sanidad es el encargado de llevar a cabo las funciones propias de la medicina escolar. La Educación para la Salud se va desarrollando con una intensa colaboración entre los responsables del Ministerio de Educación Nacional y la división de Medicina Escolar. En Austria hay coordinación entre el Departamento de Enseñanza del Ministerio Federal de Enseñanza y Arte y el Ministerio de Sanidad para llevar a cabo las actividades de información y enseñanza sanitaria en las escuelas. Polonia, mediante el Ministerio de Educación Nacional ha establecido una unidad de salud escolar con personal multiprofesional. En Grecia, es el Ministerio de Sanidad, Bienestar y Seguridad Social, a través de los Departamentos de Salud Pública, los responsables de suministrar servicios de salud escolar y de educación sanitaria. En Suecia los servicios sanitarios escolares son actividades propias de los Consejos de Condado (Landsting) y están bajo la supervisión municipal. En Portugal, los programas de salud escolar son llevados a cabo a nivel local o municipal aunque están dentro del nivel central como un área general de atención primaria de salud. Capítulo especial ocupan los Estados Unidos en cuanto a la sanidad escolar. Fue organizado en 1912. Son los Departamentos Locales de Salud (L.H.D.) los responsables de los Servicios de Salud Escolar, por otro lado, hay una necesidad ingente de promocionar la educación para la salud en toda la nación mediante una coalición de todas las partes concernientes: padres, alumnos, profesores, técnicos, políticos, etc. y asegurando un apoyo social, mejorando la preparación profesional, movilizando fondos y llevando a cabo evaluaciones. A tener presente la Salud Escolar desarrollada en países sudamericanos, en donde el enfoque inicial ha cambiado, debido a que antes consistía en dar información de un tema concreto de salud y ahora es el cambio de conducta ante esa cuestión de salud. El equipo de salud escolar es interdisciplinar así como consultor de la escuela. De otro lado, la Salud Escolar en países no desarrollados, también la he tenido en cuenta en este abordaje, y así, los principales objetivos de los programas de Salud Escolar en estos países, son: - Mejorar la condición de los niños en edad escolar en el ámbito de la salud y de la nutrición. - Mejorar el ambiente de la enseñanza escolar. - Impartir un conocimiento y habilidades más significativas en lo concerniente a la salud y nutrición. Según informes de la UNESCO, han mostrado que las condiciones actuales en las escuelas de los países en vías de desarrollo son preocupantes, no obstante, hay bastantes países en los que la Salud Escolar está naciendo poco a poco, caso de India, Kenia, Filipinas, etc. Como parte última del trabajo presento un estudio médico preventivo sobre "La Salud y la Escuela", en una comunidad educativa andaluza. Este estudio tiene tres objetivos: 1º. Estudio médico preventivo del desayuno escolar. 2º. Enfermedades transmisibles: SIDA y Escuela. 3º. Reconocimientos médicos preventivos en Educación Infantil. Del análisis de los resultados obtenidos se desprende que debe existir una mayor coordinación de todas las administraciones públicas en materia de salud escolar. Predominio del sexo femenino en la distribución total de alumnos/as, analizados, 53,09% - 3.266 alumnas frente al 46,91% - 2.087 del sexo masculino. En cuanto al desayuno escolar, decir que es "correcto" a medias, porque no es abundante ni variado y con la aparición del café en unos porcentajes del 12,65% de casos, como alimento líquido, inadecuado para estas edades. A destacar el 1,18% (36 alumnos/as) que no desayunan nada sobresaliendo como casos más frecuentes los ciclos superiores, la edad de 13 años y el sexo femenino. Existe una carencia de conocimientos en los alumnos que están cursando la Educación Secundaria Obligatoria en la zona estudiada, lo que no representa al conjunto total de la población escolar andaluza pero sí es un dato a tener en cuanta sobre el tema del SIDA y la escuela. También nos sorprenden que los alumnos demanden mayor información a través de los médicos (75,55%) y de sus profesores/as (38,14%). La patología más común detectada es la caries dental, con un 32,62%, seguido de la patología oro-faríngea con un 20,22%. Quiero decir finalmente que la educación es una herramienta potente para generar y reforzar estilos de vidas saludables. Sin embargo, la promoción de la salud escolar requiere otras actuaciones, aparte de las educativas. Por ello, hay que seguir procurando mediante medidas legislativas, económicas, urbanísticas o de otra índole, que las opciones más saludables en la vida diaria sean realmente las más fáciles de elegir, venciendo las resistencias culturales, económicas o físicas que las dificultan.
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention. ; At the Institute of Cancer Research, this work was supported by Cancer Research UK (C1298/A25514). Additional support was provided by the National Cancer Research Network. In Edinburgh, the work was supported by Programme Grant funding from Cancer Research UK (C348/A12076) and by funding for the infrastructure and staffing of the Edinburgh CRUK Cancer Research Centre. In Birmingham, funding was provided by Cancer Research UK (C6199/A16459). We are grateful to many colleagues within UK Clinical Genetics Departments (for CORGI) and to many collaborators who participated in the VICTOR, QUASAR2 and SCOT trials. We also thank colleagues from the UK National Cancer Research Network (for NSCCG). Support from the European Union [FP7/207–2013, grant 258236] and FP7 collaborative project SYSCOL and COST Action in the UK is also acknowledged [BM1206]. The COIN and COIN-B trials were funded by Cancer Research UK and the Medical Research Council and were conducted with the support of the National Institute of Health Research Cancer Research Network. COIN and COIN-B translational studies were supported by the Bobby Moore Fund from Cancer Research UK, Tenovus, the Kidani Trust, Cancer Research Wales and the National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit (2011–2014). We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z) and the Edinburgh Clinical Research Facility (ECRF) Genetics Core, Western General Hospital, Edinburgh, for the generation of genotyping data. We thank the Lothian Birth Cohorts' members, investigators, research associates, and other team members. We thank the Edinburgh Clinical Research Facility (ECRF) Genetics Core, Western General Hospital, Edinburgh, for genotyping. Lothian Birth Cohorts' data collection is supported by the Disconnected Mind project (funded by Age UK), and the Biotechnology and Biological Sciences Research Council (BBSRC, for genotyping; BB/F019394/1) and undertaken within the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (funded by the BBSRC and Medical Research Council RC as part of the LLHW [MR/K026992/1]). ET was supported by Cancer Research UK CDF (C31250/A22804). This research has been conducted using the UK Biobank Resource under Application Number 7441. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Clinical Research Facility, University of Edinburgh and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" (STRADL) [104036/Z/14/Z]). CFR was supported by a Marie Sklodowska-Curie Intra-European Fellowship Action and received considerable help from many staff in the Department of Endoscopy at the John Radcliffe Hospital in Oxford. In Finland, this work was supported by grants from the Academy of Finland [Finnish Center of Excellence Program 2012–2017, 250345 and 2018–2025, 312041], the Jane and Aatos Erkko Foundation, the Finnish Cancer Society [personal grant to K.P.], the European Research Council [ERC; 268648], the Sigrid Juselius Foundation, SYSCOL, the Nordic Information for Action eScience Center (NIASC), the Nordic Center of Excellence financed by NordForsk [project 62721, personal grant to K.P.] and State Research Funding of Kuopio University Hospital [B1401]. We acknowledge the computational resources provided by the ELIXIR node, hosted at the CSC–IT Center for Science, Finland, and funded by the Academy of Finland [grants 271642 and 263164], the Ministry of Education and Culture, Finland. V.S. was supported by the Finnish Academy [grant number 139635] and the Finnish Foundation for Cardiovascular Research. J.-P.M. was funded by The Finnish Cancer Foundation and The Jane and Aatos Erkko Foundation. Sample collection and genotyping in the Finnish Twin Cohort has been supported by the Wellcome Trust Sanger Institute, ENGAGE—European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4–2007; [grant agreement number 201413], the National Institute of Alcohol Abuse and Alcoholism [grants AA-12502 and AA-00145; to R.J.R. and K02AA018755 to D.M.D.] and the Academy of Finland [grants 100499, 205585, 265240 and 263278 to J.K.]. The work of the Colon Cancer Family Registry (CCFR) was supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under Award number U01 CA167551. The CCFR Illumina GWAS was supported by the NCI/NIH under Award Numbers U01 CA122839 and R01 CA143237 to G.C. The content of this manuscript does not necessarily reflect the views or policies of the NCI or any of the collaborating centres in the CCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CCFR. The CORSA study was funded by FFG BRIDGE (grant 829675, to A.G.), the "Herzfelder'sche Familienstiftung" (grant to A.G.) and was supported by COST Action BM1206. We kindly thank all individuals who agreed to participate in the CORSA study. Furthermore, we thank all cooperating physicians and students and the Biobank Graz of the Medical University of Graz. The DACHS study was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6–1, BR 1704/6–3, BR 1704/6–4, BR 1704/6–6 and CH 117/1–1), and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815 and 01ER1505A, 01ER1505B). We thank all participants and cooperating clinicians, and Ute Handte-Daub, Ansgar Brandhorst, Muhabbet Celik and Ursula Eilber for excellent technical assistance. The Croatian study was supported through the 10,001 Dalmatians Project, and institutional support of University Hospital for Tumours, Sestre milosrdnice University Hospital Center. James East and Simon Leedham were funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed not necessarily those of the NHS, the NIHR or the Department of Health. We acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, which was funded by the Medical Research Council Grant G0000934 and the Wellcome Trust Grant 068545/Z/02. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk. The BCAC study would not have been possible without the contributions of the following: Manjeet K. Bolla, Qin Wang, Kyriaki Michailidou and Joe Dennis. BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A16563). For the BBCS study, we thank Eileen Williams, Elaine Ryder-Mills, Kara Sargus. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) and the National Cancer Research Network (NCRN). We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). We thank the SEARCH and EPIC teams, which were funded by a programme grant from Cancer Research UK (C490/A10124) and supported by the UK NIHR BRC at the University of Cambridge. We thank Breast Cancer Now and the Institute of Cancer Research (ICR) for support and funding of the UKBGS, and the study participants, study staff, and the doctors, nurses and other health-care providers and health information sources who have contributed to the study. Genotyping of the PRACTICAL consortium OncoArray was funded by the US National Institutes of Health (NIH) [U19 CA 148537 for ELucidating Loci Involved in Prostate cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I]. Additional analytic support was provided by NIH NCI U01 CA188392 (PI: Schumacher). The PRACTICAL consortium was supported by Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, European Commission's Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2–2009–223175), and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA 148537–01 (the GAME-ON initiative). We would also like to thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, the Spanish Instituto de Salud Carlos III (ISCIII) an initiative of the Spanish Ministry of Economy and Innovation (Spain), and the Xunta de Galicia (Spain).
El trasfondo de la crisisLa abrupta abdicación del rey Juan Carlos I fue un importante aviso de que otros serios acontecimientos se preparaban en el escenario español. Curiosamente, pocos observadores intuían que hechos de similar importancia se desarrollarían a unos 600 kilómetros de distancia al este de la capital de España. Por otro lado, las incertidumbres acerca de las elecciones del Parlamento Europeo del 25 de mayo se resolvieron con la confirmación del descenso de los favores hacia los dos partidos mayoritarios españoles que se habían convertido en los sólidos cimientos de la democracia.Mientras los conservadores europeos conseguían una modesta mayoría relativa que les permitiría reforzar su reclamo de la posición de presidente de la Comisión Europea para el luxemburgués Jean Claude Juncker, en España el conservador Partido Popular y el socialista PSOE vieron carcomidos sus votos por la aparición de la novedosa formación titulada Podemos (un guiño al eslogan de Obama). Sin estructura de partido ortodoxo, se resiste a ser calificada de populista, y se ubica más allá de los socialistas y de la propia Izquierda Unida, los antiguos comunistas. En el Parlamento Europeo capturó cinco escaños en su debut. España dejaba de ser bipartidista.Pero en Madrid la preocupación obsesiva en los círculos de poder seguía siendo Catalunya. La exigencia del gobierno catalán y sus aliados (principalmente la independentista Esquerra Republicana) de celebrar un referéndum ("consulta", según el eufemismo) de independencia, programado para el 9 de noviembre, provocaba el insomnio de los conservadores españoles. Se intuía que ese problema también estaba en la mente del rey, quien resolvió optar por la abdicación y entregarle la patata caliente a su hijo, ahora ya Felipe VI. Era la manera elegante de despojarse del lastre de sus errores personales (cacería de elefantes en África, amoríos y descendencia secreta), el bajo prestigio global de la institución monárquica, y la cuestionable conducta de algunos de los vástagos. Mientras, el gobierno español tozudamente se negaba a autorizar el ejercicio por considerarlo anticonstitucional, ley en mano.Entonces estalló la "crisis Pujol", que sorprendió a todos con la guardia baja. Jordi Pujol Soley, de 83 años, el ex presidente de la autonomía catalana, que había estado en el poder durante 23 años (un tiempo récord en toda la Europa democrática) y su máximo artífice, hacía una confesión insólita. Primero informaba a su sucesor en la dirigencia del partido Convergencia de Catalunya y luego presidente de la autonomía, Artur Mas, y luego escuetamente se comunicó con los medios noticiosos. De momento, la noticia quedaba reducida a una ocultación de una herencia de su padre, convenientemente guardada durante tres décadas en Andorra. Era en realidad el preludio de un escándalo mayor. Lo que se podía haber resuelto mediante un simple informe y una modesta multa se convertía en un escándalo que a medida que pasaban las horas y los días se descubría que era en realidad la punta del iceberg de un sistema de corrupción de dimensiones de vértigo.Uniendo las denuncias de una despechada amante del primogénito de Pujol (Jordi Pujol Ferrusola) y los filtros que emanaban de algunos diarios, se comenzaba a vislumbrar una trama de corrupción en la que aparecería implicada toda la familia, incluidos los siete hijos de Pujol, su esposa, y otros allegados. El reguero de fondos y transferencias se podía rastrear a una antología de paraísos fiscales sitos en una docena de países de tres continentes. Cálculos de la judicatura y policía, convenientemente divulgados por informes periodísticos, colocan la fortuna de los Pujol al nivel de la sexta en volumen de España. Sería el producto de una red de corrupción basada en la recepción del llamado "problema del 3%" (según la famosa etiqueta plasmada por el antiguo alcalde de Barcelona, Pasqual Maragall) de comisiones ilegales. Era la "tarifa" asidua por la concesión de contratos públicos en el prioritario sector de la construcción, epicentro de la "burbuja inmobiliaria", principal causante del desastre financiero español.Las cifras que se barajan son verdaderamente espectaculares en volumen y curiosas en ciertos apartados. Por ejemplo, la documentación que están examinando las autoridades fiscales revela que el primogénito de Pujol "compró" ejemplares de Ferrari, Porche y Maserati… por apenas unos pocos $2.000. Facturas ficticias extendidas por miembros del clan reclaman servicios de intermediación de ventas de inmuebles reducidos a una llamada telefónica al coste de medio millón de euros. La reclamación del tradicional 3% fue contestada por la víctima de una "mordida" y la operación se rebajó al 1%. Cuando se produjo la explosión de la confesión inicial de Pujol, se refugió en una tríada de fincas en el Pirineo, a ambos lados de la frontera con Francia, para por fin recalar en la más modesta propiedad de verano en la población de Queralbs, desde donde trató de enviar señales de normalidad.La dimensión de corrupción proporcionaba mayor sentido a malos augurios en el contexto político. Algunas señales sutiles ya habían aparecido en el estricto nuboso horizonte catalán. Primero fue la dimisión del quinto hijo de Jordi Pujol, Oriol Pujol Ferrusola, que ocupaba el cargo de Secretario General del partido fundado por su padre. Fue una decisión forzada al agotársele al vástago todos los argumentos en su defensa por estar investigado de corrupción en concesiones públicas del servicio de inspección de automóviles. Luego se producía la retirada de Josep Antonio Durán Lleida, dirigente máximo de Unió Democrática, la formación democristiana que ha sido socia en la coalición forjada con Convergencia, con las resultantes siglas de CiU. A Durán se le reconoce una destreza diplomática notable con conexiones internacionales útiles, tanto en Cataluña como en Madrid.Catalunya es también EspañaIrónicamente, el "Molt Honorable" (título honorífico, que ahora ya no puede usar) Jordi Pujol había estado predicando durante años que su misión era la conversión de Catalunya en un "país normal", no sujeto a circunstancias excepcionales, con libertades limitadas o peculiaridades incómodas, producto de largos periodos de dictaduras. Catalunya, después de todo, según dijo una vez Pujol en Aquisgrán, bajo la sombra de Carlomagno, había sido Europa primero, no como el resto de la península, recuperada del dominio musulmán desde Asturias por los restos del reino visigodo. Ahora parecía que había conseguido la "normalidad", con un nivel de corrupción similar al existente en toda España. Ya estaría en compañía de la infanta Cristina, hija del propio rey Juan Carlos, amenazada de juicio y cárcel con su marido, el laureado jugador de "handball¨ Iñaki Urdangarín. Se podría codear con el tesorero del Partido Popular, Luis Bárcenas, cumpliendo condena en la cárcel, administrador de una contabilidad extra procedente de "mordidas", que terminaban en los bolsillos de los máximos dirigentes del partido. El escándalo Pujol coincidía con el ingreso en prisión de Jaume Matas, el ex presidente de las Baleares, y la amenaza del mismo fin para el expresidente valenciano. Catalunya, modelo de eficiencia e integridad, era ya un país normal, aunque no exactamente de la forma anhelada.Pujol en sus años de retiro disfrutaba de sueldo vitalicio superior a $100.000, tres secretarias, chófer, y un centro de estudios (con un alquiler mensual de más de $200.000, asistido por media docena de funcionarios), dedicado a temas diversos, entre ellos la ética (valor del que se enorgullecía). Ahora debía esquivar las miradas de literalmente miles de ciudadanos catalanes. Significativamente, de ellos podía recordar nombre, apellidos y fisonomía, con una memoria y capacidad política de captación y relaciones públicas sin parangón en Europa. Legiones de catalanes pueden repetir anécdotas similares en las que Pujol les preguntaba por sus hijos y nietos años más tarde de anteriores entrevistas.Pujol había construido no solamente un partido y una coalición ganadora, sino un nuevo concepto de Catalunya como nación. Era sinónima de su persona. Estaba cobijada de una ideología sincrética. Según las conveniencias, era practicante de la Democracia Cristiana, el liberalismo de genuino origen europeo, el conservadurismo tradicional tanto español como británico, e incluso la Social Democracia nórdica. Ahora todo parece que se ha evaporado. Recuérdese que esa ductilidad ideológica le había permitido disfrutar del favor personal del rey Juan Carlos (Pujol fue el primer político español al que el monarca llamó para tranquilizarle tras el fallido golpe de estado de Tejero). Rindió servicios especiales tanto al Partido Popular como al PSOE, a los que había prestado sus votos parlamentarios alternativos para permitirles gobernar.Daños colateralesA pesar de la inicial reacción de Mas ante el escándalo (la crisis era un "asunto estrictamente familiar"), la confesión de Pujol (y sus repercusiones al descubrirse el resto de la trama financiera) amenaza con terminar la propia presidencia de su "hijo político" (según su misma confesión). Peligran los planes de independencia, comenzando con la misma celebración del referéndum (ya rechazado por el gobierno español), y la desaparición de la coalición ganadora (CiU, desprovista de los democristianos de Durán) durante más de tres décadas. Mientras, por la izquierda se testifica el agrietamiento del Partido de los Socialistas de Catalunya (PSC), atenazado por el conflicto entre catalanistas y españolistas afines al PSOE, bajo la zapa de votos de Podemos. De confirmarse la negativa del gobierno español a permitir tanto un referéndum circunscrito a Catalunya como uno más amplio que cubriera todo el territorio español (alternativa no aceptable a los sectores independentistas catalanes, pues considerar que es un derecho que solamente a los catalanes pertenece), el presidente catalán ha amenazado por la celebración de una elecciones anticipadas que sería etiquetadas como plebiscitarias. Si de ese ejercicio surgiera un voto mayoritario independentista, la declaración unilateral de la secesión sería el siguiente paso, de consecuencias imprevisibles, pero que no descartan la suspensión de la autonomía catalana. Si ese ejercicio electoral se tradujera en simplemente formación de un nuevo gobierno, los sondeos muestran que Esquerra Republicana desplazaría a Convergencia.Esquerra presume merecidamente de ser la formación histórica genuinamente independentista, no como Convergencia, considerada como arribista a ese anhelo cuando Pujol asintió en dar su apoyo a esa opción. Esquerra ya había dado a Catalunya tres presidentes (Francesc Maciá, Lluís Companys –fusilado por Franco-- y Josep Tarradellas, rescatado del exilio). Pero con el predecible derrumbe de los planes independentistas, puede ser un premio de consolación en una Catalunya reducida de nuevo a una autonomía, esta vez más debilitada. Por eso se considera que Esquerra seguiría teniendo más poder e influencia en un sistema ambiguo como el actual, sin independencia y sin visos de refuerzo del autonomismo, y menos del federalismo que es la opción propuesta por los socialistas, sin que se especifique el perfil de ese sistema de tantas variantes.Todo este confuso escenario especulativo debiera aclararse durante setiembre y octubre próximos, con la apertura del Parlamento Catalán (que puede exigir a Pujol un explosivo interrogatorio), la celebración de la Diada Nacional de Catalunya, el 11 de setiembre (en conmemoración del tricentenario de la caída de Barcelona en 1714 como final de la Guerra de Sucesión, que solidificó el dominio borbónico en el trono español) y el emblemático plan del referéndum agendado para el 9 de noviembre.Pertenece al terreno de la futurología la repercusión del caso no solamente en la propia estructura política de Catalunya, sino del resto de España. Se teme que este grave incidente también contribuya a dañar más la ya deteriorada imagen de la transición española, hasta hace muy poco, modelo internacional de pacífica reconstrucción de la democracia en otras regiones del planeta. Con el tejido constitucional español bajo cuestionamiento, ahora solamente falta este daño al entramado social. De rebote, convendrá meditar sobre el impacto de una España diferente, con o sin Catalunya, en el mismo entramado de la Unión Europea, ya de por sí atenazada por otros conatos secesionistas (como en Escocia). Si los dirigentes europeos en su mayoría temían la disgregación del territorio español, tampoco ahora darían la bienvenida a una debilitada España por una mayor trama de corrupción de la ya existente. Joaquín Roy es Catedrático 'Jean Monnet' Director del Centro de la Unión Europea Universidad de Miami
Me planteo el hecho de que la Medicina, Salud o Higiene Escolar ha existido desde hace mucho tiempo, y que las interrelaciones entre la Salud y la Educación han tenido unos lazos de unión muy fuertes. A lo largo de todo este trabajo se puede perfectamente corroborar, ya que desde la época romana, árabe, etc. hasta nuestros días, existen datos a tener en cuenta y presente cuando tengamos que analizar la Medicina, Salud o Higiene Escolar. Destacar cómo el estilo de vida de la población y el medio ambiente, son las dos grandes causas que explican la mayoría de los problemas de salud del mundo desarrollado, así como que las acciones de Salud pasan por la prevención de enfermedad y la promoción de la Salud. Pues bien, dentro de esta última destaco la importancia de instaurar políticas alternativas de promoción de la salud ya desde la escuela, para modificar las actitudes y comportamiento de la población. Sin olvidar la participación y el diálogo con el profesor, elementos básicos en el aprendizaje de la salud. Por otra parte, la situación particular del Homo Sapiens en relación con sus problemas de salud/enfermedad viene especialmente configurada por su naturaleza sociocultural, la cual le capacita para transformar su medio, para transformarse a sí mismo y para desarrollar nuevos comportamientos. En el ejercicio de esta capacidad adquiere una importancia esencial el proceso educativo. Teniendo en cuenta lo anterior, en la reforma educativa y en sus aspectos curriculares aparece la salud y sus contenidos desarrollados. Salud que la debemos entender como un valor a cultivar en la escuela, que permita una vida sana y una población bien formada y más equilibrada. Se constata que el marco teórico de la Medicina Escolar española es desolador y mísero, viene reflejado por innumerables autores y escritores de la época, y así por un lado, la escuela que existe a principios del siglo XIX "no sirve para nada", "aparte que son pocas". "Las escuelas de la mayor parte de los pueblos españoles son locales sin luz y sin ventilación, donde los niños pierden en su desarrollo físico lo que pueden ganar en su desarrollo intelectual". Azorín publicó en 1908 "Los hijos de España" en donde se expresaba así: "En esta España no hay escuelas, los niños no pueden aprender a leer y escribir. Las escuelas que existen son antihigiénicas y lóbregas". Las conclusiones que se sacan del panorama educativo español durante el siglo XIX no pueden ser más claras: En primer lugar, sólo una minoría de niños tuvo acceso a la enseñanza, de entre estos, únicamente los mejor dotados económicamente pudieron hacer algún ejercicio físico, aunque de un marcado carácter militarista. En segundo lugar, destaca la ausencia de niñas en todos los aspectos higiénicos. En tercer lugar, la alimentación era pobre y la higiene escasa, y, por último, las materias de enseñanza inapropiadas. Vista la precaria situación de la escuela española así como la de la pedagogía sanitaria existente y paradójicamente, en comparación con otras actividades, España se ha caracterizado por su temprana capacidad para detectar la problemática sanitaria escolar en relación con otros países europeos. Así, las primeras normas oficiales de que tengamos noticia en España referidas a la Sanidad Escolar, datan de hace más de dos siglos, hacia 1770, y están incluidas en la Novísima Recopilación de las Leyes de España, Libro VII, Título Primero: "De las escuelas y maestros de primeras letras y de educación de niños". Sin embargo, las normas legales sobre Medicina, Sanidad e Higiene Escolar, consideradas en el conjunto de la legislación acerca de la enseñanza, extremadamente rica en toda clase de disposiciones, decretos, órdenes, regulaciones, etc., es más bien pobre y sobre todo teórica. Importante fue la creación en 1911 de la Inspección médico-escolar del Estado, por el doctor Tolosa Latour. Tuvo su refrendo legal en el real decreto de 16 de Junio de 1911, a través del Ministerio de Instrucción Pública y Bellas Artes. En el año 1975 aparece el Reglamento Provisional de Sanidad Escolar y en el año 1978, el decreto sobre Ordenación de los Servicios de Medicina e Higiene Escolar. Declarado nulo y sin ningún valor por el Tribunal Supremo, en una sentencia dictada el día 1 de diciembre de 1982. Ahora bien, todo esto sufre un cambio bastante brusco, pues hemos de tener en cuenta la aparición de las distintas Comunidades Autónomas, con la transferencia de competencias que ello conlleva. Así cada Autonomía tiene sus decretos, órdenes, leyes sobre Salud Escolar. De todas las Autonomías, decir que hay leyes sobre Salud Escolar en Aragón, Principado de Asturias, Extremadura, Galicia, Gobierno Vasco y en La Rioja. En las restantes Comunidades existen órdenes, decretos e incluso las actividades de Salud Escolar son incluidas en programas de Atención Primaria de Salud. En referencia a la Sanidad, Medicina e Higiene Escolar desarrollada en otros países, destaca la figura de Bernardo Ramazzini da Caspi, promotor de los orígenes de la medicina social. Johan Peter Frank, considerado como el fundador de la higiene pública, pasando por Jean Jacques Rousseau, que debemos erigir como el auténtico origen de la Medicina Escolar. En Europa, comenzamos con Inglaterra donde se cuida bastante a la Salud, Medicina o Higiene de los escolares. Se crea el Servicio de Sanidad Escolar de Inglaterra en 1974. La educación para la salud se considera parte del plan de estudio escolar. Algo parecido ocurre en Francia, donde el control médico de los escolares fue planteado sin duda por primera vez en el mundo, durante la Revolución Francesa de 1789. Italia posee unos Servicios de Salud Escolar municipales, en donde el médico escolar trabaja en un equipo multidisciplinar. En Holanda son los municipios o grupos de municipios que están asociados, los obligados por ley a tener un Servicio municipal de salud escolar. En la República Federal de Alemania, la salud escolar y la educación para la salud son objetivos principales del Servicio de Salud Pública (S.S.P.). Su financiación proviene principalmente del municipio (Gemeindem) y del estado (Laender). Bélgica tiene un programa para el control médico y psicológico de la población escolar, llevado a cabo por el Ministerio de Educación. En Dinamarca, son los municipios los responsables del examen médico de todos los preescolares y escolares. El médico escolar y la enfermera participan junto con los maestros en la educación para la salud escolar. En Luxemburgo, el Ministerio de Sanidad es el encargado de llevar a cabo las funciones propias de la medicina escolar. La Educación para la Salud se va desarrollando con una intensa colaboración entre los responsables del Ministerio de Educación Nacional y la división de Medicina Escolar. En Austria hay coordinación entre el Departamento de Enseñanza del Ministerio Federal de Enseñanza y Arte y el Ministerio de Sanidad para llevar a cabo las actividades de información y enseñanza sanitaria en las escuelas. Polonia, mediante el Ministerio de Educación Nacional ha establecido una unidad de salud escolar con personal multiprofesional. En Grecia, es el Ministerio de Sanidad, Bienestar y Seguridad Social, a través de los Departamentos de Salud Pública, los responsables de suministrar servicios de salud escolar y de educación sanitaria. En Suecia los servicios sanitarios escolares son actividades propias de los Consejos de Condado (Landsting) y están bajo la supervisión municipal. En Portugal, los programas de salud escolar son llevados a cabo a nivel local o municipal aunque están dentro del nivel central como un área general de atención primaria de salud. Capítulo especial ocupan los Estados Unidos en cuanto a la sanidad escolar. Fue organizado en 1912. Son los Departamentos Locales de Salud (L.H.D.) los responsables de los Servicios de Salud Escolar, por otro lado, hay una necesidad ingente de promocionar la educación para la salud en toda la nación mediante una coalición de todas las partes concernientes: padres, alumnos, profesores, técnicos, políticos, etc. y asegurando un apoyo social, mejorando la preparación profesional, movilizando fondos y llevando a cabo evaluaciones. A tener presente la Salud Escolar desarrollada en países sudamericanos, en donde el enfoque inicial ha cambiado, debido a que antes consistía en dar información de un tema concreto de salud y ahora es el cambio de conducta ante esa cuestión de salud. El equipo de salud escolar es interdisciplinar así como consultor de la escuela. De otro lado, la Salud Escolar en países no desarrollados, también la he tenido en cuenta en este abordaje, y así, los principales objetivos de los programas de Salud Escolar en estos países, son: - Mejorar la condición de los niños en edad escolar en el ámbito de la salud y de la nutrición. - Mejorar el ambiente de la enseñanza escolar. - Impartir un conocimiento y habilidades más significativas en lo concerniente a la salud y nutrición. Según informes de la UNESCO, han mostrado que las condiciones actuales en las escuelas de los países en vías de desarrollo son preocupantes, no obstante, hay bastantes países en los que la Salud Escolar está naciendo poco a poco, caso de India, Kenia, Filipinas, etc. Como parte última del trabajo presento un estudio médico preventivo sobre "La Salud y la Escuela", en una comunidad educativa andaluza. Este estudio tiene tres objetivos: 1º. Estudio médico preventivo del desayuno escolar. 2º. Enfermedades transmisibles: SIDA y Escuela. 3º. Reconocimientos médicos preventivos en Educación Infantil. Del análisis de los resultados obtenidos se desprende que debe existir una mayor coordinación de todas las administraciones públicas en materia de salud escolar. Predominio del sexo femenino en la distribución total de alumnos/as, analizados, 53,09% - 3.266 alumnas frente al 46,91% - 2.087 del sexo masculino. En cuanto al desayuno escolar, decir que es "correcto" a medias, porque no es abundante ni variado y con la aparición del café en unos porcentajes del 12,65% de casos, como alimento líquido, inadecuado para estas edades. A destacar el 1,18% (36 alumnos/as) que no desayunan nada sobresaliendo como casos más frecuentes los ciclos superiores, la edad de 13 años y el sexo femenino. Existe una carencia de conocimientos en los alumnos que están cursando la Educación Secundaria Obligatoria en la zona estudiada, lo que no representa al conjunto total de la población escolar andaluza pero sí es un dato a tener en cuanta sobre el tema del SIDA y la escuela. También nos sorprenden que los alumnos demanden mayor información a través de los médicos (75,55%) y de sus profesores/as (38,14%). La patología más común detectada es la caries dental, con un 32,62%, seguido de la patología oro-faríngea con un 20,22%. Quiero decir finalmente que la educación es una herramienta potente para generar y reforzar estilos de vidas saludables. Sin embargo, la promoción de la salud escolar requiere otras actuaciones, aparte de las educativas. Por ello, hay que seguir procurando mediante medidas legislativas, económicas, urbanísticas o de otra índole, que las opciones más saludables en la vida diaria sean realmente las más fáciles de elegir, venciendo las resistencias culturales, económicas o físicas que las dificultan. Gracias a mi experiencia personal, desarrollada durante más de ocho cursos escolares, tengo a bien hacer las consideraciones siguientes: 1ª. Que las acciones de salud pasan por una prevención de la enfermedad y por la promoción de la salud. Dentro de esta última destaco el hecho de promocionar la salud ya desde la escuela para modificar actitudes y comportamientos de la población en estas edades iniciales de su vida. 2ª. España se ha caracterizado por su temprana capacidad para detectar la problemática sanitaria escolar en relación con otros países. Sin embargo, las normas legales sobre Medicina, Salud o Higiene Escolar, extremadamente rica en teoría, es considerada pobre a la hora de poner en práctica lo anterior. 3ª. Los programas de Medicina o Salud Escolar deben acompañarse de una buena política y soporte económico que posibilite su independencia en el marco del medio escolar, capacitando a los alumnos/as para que puedan elegir conscientemente su estilo de vida. 4ª. La salud es un valor a cultivar en la escuela, que debe tratarse como un objetivo dentro del Plan educativo de Centro, con un contenido de una materia que ocupará una parcela determinada en el total del curriculum. Haciéndolo así, formaremos hábitos saludables y una población más equilibrada. 5ª. Vacío legislativo a nivel de la Comunidad Andaluza en materia de Promoción de la Salud en la Escuela. No hay una ley de Salud Escolar, causante del desfase que padecemos en relación a otras comunidades autónomas que sí la poseen. Así se podrían resolver definitivamente las actuales deficiencias en esta materia de Salud Escolar. 6ª. La Medicina Escolar tiene un papel destacadísimo para el control del absentismo de los trabajadores de la enseñanza, a través de una adecuada información y formación sobre las condiciones de trabajo, así como en la elaboración de normas preventivas de seguridad e higiene sobre patologías comunes dentro de este medio escolar. 7ª. Progresiva intervención conjunta y coordinada entre los Médicos de los Servicios de Apoyo Escolar y los Asesores-Inspectores Médicos de la Delegación Provincial de Educación en materia de Salud Laboral del docente y no docente. 8ª. Mi experiencia y el trabajo desempeñado en el ámbito escolar, me ha permitido constatar la demanda que los profesores/as, padres/madres y los alumnos/as hacen al médico del equipo en función del apoyo educativo que proporcionan. 9ª. Que la figura profesional el médico en la escuela no sea, como era tradicionalmente, un agente externo, sino un eslabón más dentro de la cadena del sistema educativo. Es una intervención directa y desde dentro del organigrama de educación. 10ª. Promocionado la Salud Escolar a través de la colaboración y el asesoramiento al profesorado, Centro de Profesores y otros miembros docentes, en la incorporación de la Educación para la Salud al curriculum escolar, teniendo en cuenta la orientación técnica precisa para alumnos/as y padres/madres. 11ª. Coordinación con los servicios sanitarios, sociales, comunitarios y educativos o instituciones públicas y privadas que incidan en el alumno/a, estableciendo un sistema de canalización de alumnos con sospecha de padecer alguna patología a los servicios especializados, actuando el médico del equipo de apoyo escolar como interlocutor. Ello redundaría en cuestiones de tiempo, eficacia y dinero. 12ª. Se deben elaborar informes y documentos médicos escolares que promocionen la investigación médica en el medio escolar. 13ª. Se detecta la necesidad imperiosa de que la Medicina Escolar desarrollada por nosotros tenga cada día más auge para que los médicos de educación, en colaboración y coordinación con los servicios sanitarios, sociales y comunitarios, sea una realidad por el bien de la población escolar andaluza.
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis. ; he authors in this manuscript were working on behalf of BCAC, CCFR, CIMBA, CORECT, GECCO, OCAC, PRACTICAL, CRUK, BPC3, CAPS, PEGASUS, TRICL- ILCCO, ABCTB, APCB, BCFR, CONSIT TEAM, EMBRACE, GC-HBOC, GEMO, HEBON, kConFab/AOCS Mod SQuaD, and SWE-BRCA. The breast cancer genome-wide association analyses: BCAC is funded by Cancer Research UK [C1287/A16563, C1287/ A10118], the European Union ' s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST, respectively), and by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/ A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de lÉconomie, Science et Innovation du Québec through Genome Québec and the PSR-SIIRI-701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community 's Seventh Framework.Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112 — the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily re fl ect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Aus- tralia), and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) is generously supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The ACP study is funded by the Breast Cancer Research Trust, UK. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia and acknowledges funding from the National Breast Cancer Foundation (JS). For the BCFR-NY, BCFR-PA, and BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily re fl ect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. For BIGGS, ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy ' s & St. Thomas ' NHS Foundation Trust in partnership with King ' s College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. BOCS is supported by funds from Cancer Research UK (C8620/A8372/A15106) and the Institute of Cancer Research (UK). BOCS acknowledges NHS funding to the Royal Marsden/Institute of Cancer Research NIHR Specialist Cancer Biomedical Research Centre. The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Co fi nanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + DeI + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Gali- cia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CAMA study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) (SALUD-2002- C01-7462). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l ' Alimentation, de l ' Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario (PI11/00923 and PI12/00070). COLBCCC is sup- ported by the German Cancer Research Center (DKFZ), Heidelberg, Germany. D.T. was in part supported by a postdoctoral fellowship from the Alexander von Humboldt Foundation. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. H.A.C eceives support from the Lon V Smith Foundation (LVS39420). The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charit.No. 1121258 and the NCRN. The coordination of EPIC is fi nancially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l ' Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Neth- erlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC- Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC- Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Kreb- shilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (Ger- man Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713- 241202, 713-241202, 14505/2470, and 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). GLACIER was supported by Breast Cancer Now, CRUK and Biomedical Research Centre at Guy ' s and St Thomas ' NHS Foundation Trust and King ' s College London. The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf- Bartling Foundation. The HEBCS was fi nancially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HERPACC was supported by MEXT Kakenhi (No. 170150181 and 26253041) from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan, by National Cancer Center Research and Development Fund, and " Practical Research for Innovative Cancer Control (15ck0106177h0001) " from Japan Agency for Medical Research and develop- ment, AMED, and Cancer Bio Bank Aichi. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scienti fi c Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014, and 17-44-020498. ICICLE was supported by Breast Cancer Now, CRUK, and Biomedical Research Centre at Guy ' s and St Thomas ' NHS Foundation Trust and King ' s College London. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (A.L. F.) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was fi nancially supported by the special Government Funding (E.V. O.) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). G.C.-T. and P.W. are supported by the NHMRC. RB was a Cancer Institute NSW Clinical Research Fellow. The KOHBRA study was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 1020350; 1420190). LAABC is supported by grants (1RB-0287, 3PB- 0102, 5PB-0018, 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. TheCSP is also part of the National Cancer Institute ' s Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. L.M.B.C. is supported by the ' Stichting tegen Kanker ' . D.L. is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology " Georgi D. Efremov " and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Edu- cation and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects " 5 × 1000 " ). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839, and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foun- dation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286, and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the " CIHR Team in Familial Risks of Breast Cancer " program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. MYBRCA is funded by research grants from the Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/ 06) and Cancer Research Malaysia. MYMAMMO is supported by research grants from Yayasan Sime Darby LPGA Tournament and Malaysian Ministry of Higher Education (RP046B-15HTM). The NBCS has been supported by the Research Council of Norway grant 193387/V50 (to A.-L. Børresen-Dale and V.N. Kristensen) and grant 193387/H10 (to A.-L. Børresen-Dale and V.N. Kristensen), South Eastern Norway Health Authority (grant 39346 to A.-L. Børresen-Dale and 27208 to V.N. Kristensen) and the Norwegian Cancer Society (to A.-L. Børresen-Dale and 419616 - 71248 - PR-2006-0282 to V.N. Kristensen). It has received funding from the K.G. Jebsen Centre for Breast Cancer Research (2012-2015). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC- BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manu- script does not necessarily re fl ect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, and U01 CA179715), and the North Carolina University Cancer Research Fund. The NGOBCS was supported by Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scienti fi c Research on Priority Areas, 17015049 and for Scienti fi c Research on Innovative Areas, 221S0001, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation, and the special Governmental EVO funds for Oulu University Hospital-based research activities. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997- 1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI- NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/ A11699, C1275/C22524, C1275/A19187, C1275/A15956, and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, UMCA182910, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scienti fi c development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME- ON) Network U19 CA148065. The SBCS was supported by Shef fi eld Experimental Cancer Medicine Centre and Breast Cancer Now Tissue Bank. The SCCS is supported by a grant from the National Institutes of Health (R01 CA092447). Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health, Of fi ce of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR 72205. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the of fi cial views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by Cancer Research UK [C490/A10124, C490/ A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347). SGBCC is funded by the NUS start- up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/1/21/19/425. The Sister Study (SIS- TER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The TBCS was funded by The National Cancer Institute, Thailand. The TNBCC was supported by a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Bio- medical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The US3SS study was supported by Massachusetts (K.M.E., R01CA47305), Wisconsin (P.A.N., R01 CA47147) and New Hampshire (L.T.-E., R01CA69664) centers, and Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WAABCS study was supported by grants from the National Cancer Institute of the National Institutes of Health (R01 CA89085 and P50 CA125183 and the D43 TW009112 grant), Susan G. Komen (SAC110026), the Dr. Ralph and Marian Falk Medical Research Trust, and the Avon Foundation for Women. The WHI program is funded by the National Heart, Lung, and Blood Institute, the US National Institutes of Health and the US Department of Health and Human Services (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). This work was also funded by NCI U19 CA148065-01. D.G.E. is supported by the all Manchester NIHR Biomedical research center Manchester (IS-BRC- 1215-20007). HUNBOCS, Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grant KTIA-OTKA CK-80745, NKFI_OTKA K-112228. C.I. received support from the Nontherapeutic Subject Registry Shared Resource at George- town University (NIH/NCI P30-CA-51008) and the Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research. K.M. is supported by CRUK C18281/ A19169. City of Hope Clinical Cancer Community Research Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J Weitzel) from the National Cancer Institute and the of fi ce of the Directory, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the of fi cial views of the National Institutes of Health. The colorectal cancer genome-wide association analyses: Colorectal Transdisciplinary Study (CORECT): The content of this manuscript does not necessarily re fl ect the views or policies of the National Cancer Institute or any of the collaborating centers in the CORECT Consortium, nor does mention of trade names, commercial products or organizations imply endor- sement by the US Government or the CORECT Consortium. We are incredibly grateful for the contributions of Dr. Brian Henderson and Dr. Roger Green over the course of this study and acknowledge them in memoriam. We are also grateful for support from Daniel and Maryann Fong. ColoCare: we thank the many investigators and staff who made thisHHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN26 8201600004C. The head and neck cancer genome-wide association analyses: The study was supported by NIH/NCI: P50 CA097190, and P30 CA047904, Canadian Cancer Society Research Institute (no. 020214) and Cancer Care Ontario Research Chair to R.H. The Princess Margaret Hospital Head and Neck Cancer Translational Research Program is funded by the Wharton family, Joe ' s Team, Gordon Tozer, Bruce Galloway and the Elia family. Geoffrey Liu was supported by the Posluns Family Fund and the Lusi Wong Family Fund at the Princess Margaret Foundation, and the Alan B. Brown Chair in Molecular Genomics. This publication presents data from Head and Neck 5000 (H&N5000). H&N5000 was a component of independent research funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Human papillomavirus (HPV) in H&N5000 serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). National Cancer Institute (R01-CA90731); National Institute of Environmental Health Sciences (P30ES10126). The authors thank all the members of the GENCAPO team/The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). CPS-II recruitment and maintenance is supported with intramural research funding from the American Cancer Society. Genotyping per- formed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1 × 01HG007780- 0. The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/ 12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19-CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the Eur- opean Commission ' s 5th Framework Program (QLK1-2001-00182), the Italian Associa- tion for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222). The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to S.B., and Fon- dazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cienti fi ca y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). We thank Leticia Fernandez, Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba and Sergio and Rosalina Koifman, for their efforts with the IARC Latin America study São Paulo center. The IARC Central Europe study was supported by European Commission ' s INCO- COPERNICUS Program (IC15- CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28. The IARC Oral Cancer Multicenter study was funded by grant S06 96 202489 05F02 from Europe against Cancer; grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is fi nancially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The lung cancer genome-wide association analyses: Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by (U19-CA148127, CA148127S1, U19CA203654, and Cancer Prevention Research Institute of Texas RR170048). The ILCCO data harmonization is supported by Cancer Care Ontario Research Chair of Population Studies to R. H. and Lunenfeld-Tanenbaum Research Institute, Sinai Health System. The TRICL-ILCCO OncoArray was supported by in-kind genotyping by the Centre for Inherited Disease Research (26820120008i-0-26800068-1). The CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03-0365, and FIS- 07-BI060604, FICYT/Asturias grant numbers FICYT PB02-67 and FICYT IB09-133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiologia y Salud Pública. CIBERESP, SPAIN. The work performed in the CARET study was supported by the National Institute of Health/National Cancer Insti- tute: UM1 CA167462 (PI: Goodman), National Institute of Health UO1-CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA151989-01A1(PI Doherty). The Liverpool Lung project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578, CA074386. The Multi-ethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464, and CA148127. The work performed in MSH-PMH study was supported by The Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. NJLCS was funded by the State Key Program of National Natural Science ofChina (81230067), the National Key Basic Research Program Grant (2011CB503805), the Major Program of the National Natural Science Foundation of China (81390543). The Norway study was supported by Norwegian Cancer Society, Norwegian Research Council. The Shanghai Cohort Study (SCS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The Singapore Chinese Health Study (SCHS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The work in TLC study has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997), and by a Cancer Center Support Grant (CCSG) at the H. Lee Mof fi tt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30- CA76292). The Vanderbilt Lung Cancer Study — BioVU dataset used for the analyses described was obtained from Vanderbilt University Medical Center ' s BioVU, which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the Vanderbilt CTSA grant UL1TR000445 from NCATS/NIH. Dr. Aldrich was supported by NIH/National Cancer Institute K07CA172294 (PI: Aldrich) and Dr. Bush was sup- ported by NHGRI/NIH U01HG004798 (PI: Crawford). The Copenhagen General Population Study (CGPS) was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The Kentucky Lung Cancer Research Initiative was supported by the Department of Defense [Congressionally Directed Medical Research Program, U.S. Army Medical Research and Materiel Com- mand Program] under award number: 10153006 (W81XWH-11-1-0781). Views and opinions of, and endorsements by the author(s) do not re fl ect those of the US Army or the Department of Defense. This research was also supported by unrestricted infrastructure funds from the UK Center for Clinical and Translational Science, NIH grant UL1TR000117 and Markey Cancer Center NCI Cancer Center Support Grant (P30 CA177558) Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics. The M.D. Anderson Cancer Center study was supported in part by grants from the NIH (P50 CA070907, R01 CA176568) (to X.W.), Cancer Prevention & Research Institute of Texas (RP130502) (to X. W.), and The University of Texas MD Anderson Cancer Center institutional support for the Center for Translational and Public Health Genomics. The deCODE study of smoking and nicotine dependence was funded in part by a grant from NIDA (R01- DA017932). The study in Lodz center was partially funded by Nofer Institute of Occupational Med- icine, under task NIOM 10.13: Predictors of mortality from non-small cell lung cancer — fi eld study. Genetic sharing analysis was funded by NIH grant CA194393. The research undertaken by M.D.T., L.V.W., and M.S.A. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.D.T. holds a Medical Research Council Senior Clinical Fellowship (G0902313). The work to assemble the FTND GWAS meta-analysis was supported by the National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA) grant number R01 DA035825 (Prin- cipal Investigator [PI]: DBH). The study populations included COGEND (dbGaP phs000092.v1.p1 and phs000404.v1.p1), COPDGene (dbGaP phs000179.v3.p2), deCODE Genetics, EAGLE (dbGaP phs000093.vs.p2), and SAGE. dbGaP phs000092.v1.p1). See Hancock et al. Transl Psychiatry 2015 (PMCID: PMC4930126) for the full listing of funding sources and other acknowledgments. The Resource for the Study of Lung Cancer Epidemiology in North Trent (ReSoLuCENT)study was funded by the Shef fi eld Hospitals Charity, Shef fi eld Experimental Cancer Medicine Centre and Weston Park Hospital Cancer Charity. The ovarian cancer genome-wide association analysis: The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scienti fi c development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The OCAC OncoArray genotyping project was funded through grants from the U.S. National Institutes of Health (CA1X01HG007491-01 (C.I.A.), U19-CA148112 (T.A.S.), R01-CA149429 (C.M.P.), and R01-CA058598 (M.T.G.); Canadian Institutes of Health Research (MOP-86727 (L.E.K.) and the Ovarian Cancer Research Fund (A.B.). The COGS project was funded through a European Commission ' s Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175) and through a grant from the U.S. National Insti- tutes of Health (R01-CA122443 (E.L.G)). Funding for individual studies: AAS: National Institutes of Health (RO1-CA142081); AOV: The Canadian Institutes for Health Research (MOP-86727); AUS: The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600, 400413 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tas- mania and Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182). The Australian Ovarian Cancer Study gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation; BAV: ELAN Funds of the University of Erlangen-Nuremberg; BEL: National Kankerplan; BGS: Breast Cancer Now, Institute of Cancer Research; BVU: Vanderbilt CTSA grant from the National Institutes of Health (NIH)/National Center for Advancing Translational SciencesNCATS) (ULTR000445); CAM: National Institutes of Health Research Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Cancer Centre; CHA: Innovative Research Team in University (PCSIRT) in China (IRT1076); CNI: Instituto de Salud Carlos III (PI12/01319); Ministerio de Economía y Competitividad (SAF2012); COE: Department of Defense (W81XWH-11-2-0131); CON: National Institutes of Health (R01-CA063678, R01-CA074850; and R01-CA080742); DKE: Ovarian Cancer Research Fund; DOV: National Institutes of Health R01-CA112523 and R01-CA87538; EMC: Dutch Cancer Society (EMC 2014-6699); EPC: The coordination of EPIC is fi nancially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l ' Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC- Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom); GER: German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB 9401) and the German Cancer Research Center (DKFZ); GRC: This research has been co- fi nanced by the European Union (European Social Fund — ESF) and Greek national funds through the Operational Program " Education and Lifelong Learn- ing " of the National Strategic Reference Framework (NSRF) — Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund; GRR: Roswell Park Cancer Institute Alliance Foundation, P30 CA016056; HAW: U.S. National Institutes of Health (R01- CA58598, N01-CN-55424, and N01-PC-67001); HJO: Intramural funding; Rudolf- Bartling Foundation; HMO: Intramural funding; Rudolf-Bartling Foundation; HOC: Helsinki University Research Fund; HOP: Department of Defense (DAMD17-02-1-0669) and NCI (K07-CA080668, R01-CA95023, P50-CA159981 MO1-RR000056 R01- CA126841); HUO: Intramural funding; Rudolf-Bartling Foundation; JGO: JSPS KAKENHI grant; JPN: Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare; KRA: This study (Ko-EVE) was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 0920010); LAX: American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; LUN: ERC-2011-AdG 294576-risk factors cancer, Swedish Cancer Society, Swedish Research Council, Beta Kamprad Foundation; MAC: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; Fraternal Order of Eagles; MAL: Funding for this study was provided by research grant R01- CA61107 from the National Cancer Institute, Bethesda, MD, research grant 94 222 52 from the Danish Cancer Society, Copenhagen, Denmark; and the Mer- maid I project; MAS: Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; MAY: National Institutes of Health (R01- CA122443, P30-CA15083, and P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; MCC: Cancer Council Victoria, National Health and Medical Research Council of Australia (NHMRC) grants number 209057, 251533, 396414, and 504715; MDA: DOD Ovarian Cancer Research Program (W81XWH-07-0449); MEC: NIH (CA54281, CA164973, CA63464); MOF: Mof fi tt Cancer Center, Merck Pharmaceuticals, the state of Florida, Hillsborough County, and the city of Tampa; NCO: National Institutes of Health (R01-CA76016) and the Department of Defense (DAMD17-02-1-0666); NEC: National Institutes of Health R01- CA54419 and P50-CA105009 and Department of Defense W81XWH-10-1-02802; NHS: UM1 CA186107, P01 CA87969, R01 CA49449, R01-CA67262, UM1 CA176726; NJO: National Cancer Institute (NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, and P30-CA072720) and the Cancer Institute of New Jersey; If Sara Olson and/or Irene Orlow is a co-author, please add NCI CCSG award (P30-CA008748) to the funding sources; NOR: Helse Vest, The Norwegian Cancer Society, The Research Council of Norway; NTH: Radboud University Medical Centre; OPL: National Health and Medical Research Council (NHMRC) of Australia (APP1025142) and Brisbane Women ' s Club; ORE: OHSU Foundation; OVA: This work was supported by Canadian Institutes of Health Research grant (MOP-86727) and by NIH/NCI 1 R01CA160669-01A1; PLC: Intramural Research Program of the National Cancer Institute; POC: Pomeranian Medical Uni- versity; POL: Intramural Research Program of the National Cancer Institute; PVD: Canadian Cancer Society and Cancer Research Society GRePEC Program; RBH: National Health and Medical Research Council of Australia; RMH: Cancer Research UK, Royal Marsden Hospital; RPC: National Institute of Health (P50-CA159981, R01-CA126841); SEA: Cancer Research UK (C490/A10119 C490/A10124); UK National Institute forHealth Research Biomedical Research Centres at the University of Cambridge; SIS: NIH, National Institute of Environmental Health Sciences, Z01-ES044005 and Z01-ES049033; SMC: The bbSwedish Research Council-SIMPLER infrastructure; the Swedish Cancer Foundation; SON: National Health Research and Development Program, Health Canada, grant 6613-1415-53; SRO: Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589); STA: NIH grants U01 CA71966 and U01 CA69417; SWE: Swedish Cancer foundation, WeCanCureCancer and VårKampMotCancer foundation; SWH: NIH (NCI) grant R37-CA070867; TBO: National Institutes of Health (R01-CA106414-A2), American Cancer Society (CRTG-00-196-01- CCE), Department of Defense (DAMD17-98-1-8659), Celma Mastery Ovarian Cancer Foundation; TOR: NIH grants R01-CA063678 and R01 CA063682; UCI: NIH R01- CA058860 and the Lon V Smith Foundation grant LVS39420; UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure; UKO: The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre; UKR: Cancer Research UK (C490/A6187), UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; USC: P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403, and Cali- fornia Cancer Research Program (00-01389V-20170, 2II0200); VAN: BC Cancer Foun- dation, VGH & UBC Hospital Foundation; VTL: NIH K05-CA154337; WMH: National Health and Medical Research Council of Australia, Enabling Grants ID 310670 & ID 628903. Cancer Institute NSW Grants 12/RIG/1-17 & 15/RIG/1-16; WOC: National Science Centren (N N301 5645 40). The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academia Reserve. The prostate cancer genome-wide association analyses: we pay tribute to Brian Henderson, who was a driving force behind the OncoArray project, for his vision and leadership, and who sadly passed away before seeing its fruition. We also thank the individuals who participated in these studies enabling this work. The ELLIPSE/ PRACTICAL (http//:practical.icr.ac.uk) prostate cancer consortium and his collaborating partners were supported by multiple funding mechanisms enabling this current work. ELLIPSE/PRACTICAL Genotyping of the OncoArray was funded by the US National Institutes of Health (NIH) (U19 CA148537 for ELucidating Loci Involved in Prostate Cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I). Additional analytical support was provided by NIH NCI U01 CA188392 (F.R.S.). Funding for the iCOGS infrastructure came from the European Community ' s Seventh Framework Pro- gramme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/ A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112; the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This work was supported by the Canadian Institutes of Health Research, European Commission ' s Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/ A3354, C5047/A10692, C16913/A6135, C5047/A21332 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA148537-01 (the GAME-ON initiative). We also thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Founda- tion, Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network UK, and The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. The Prostate Cancer Program of Cancer Council Victoria also acknowledge grant support from The National Health and Medical Research Council, Australia (126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394, and 614296), VicHealth, Cancer Council Victoria, The Prostate Cancer Foun- dation of Australia, The Whitten Foundation, PricewaterhouseCoopers, and Tattersall ' s. E.A.O., D.M.K., and E.M.K. acknowledge the Intramural Program of the National Human Genome Research Institute for their support. The BPC3 was supported by the U.S. National Institutes of Health, National Cancer Institute (cooperative agreements U01- CA98233 to D.J.H., U01-CA98710 to S.M.G., U01-CA98216 to E.R., and U01-CA98758 to B.E.H., and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics). CAPS GWAS study was supported by the Swedish Cancer Foundation (grant no 09-0677, 11-484, 12-823), the Cancer Risk Prediction Center (CRisP; www.crispcenter.org ), a Linneus Centre (Contract ID 70867902) fi nanced by the Swedish Research Council, Swedish Research Council (grant no K2010-70 × - 20430-04-3, 2014-2269). The Hannover Prostate Cancer Study was supported by the Lower Saxonian Cancer Society. PEGASUS was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. RAPPER was supported by the NIHR Manchester Bio- medical Research Center, Cancer Research UK (C147/A25254, C1094/A18504) and the EUs7Framework Programme Grant/Agreement no 60186. Overall: this research has been conducted using the UK Biobank Resource (application number 16549). NHS is supported by UM1 CA186107 (NHS cohort infrastructure grant), P01 CA87969, and R01 CA49449. NHSII is supported by UM1 CA176726 (NHSII cohort infrastructure grant),and R01-CA67262. A.L.K. is supported by R01 MH107649. We would like to thank the participants and staff of the NHS and NHSII for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. ; Sí
L'oggetto di questa tesi è la peculiare comparsa del termine imperator in un numero esiguo, ma comunque significativo di documenti provenienti dal regno di Asturia e León e dalla Britannia del X secolo. Se già di per sé questa sorta di "incongruenza storica" cattura l'attenzione, il fatto che i due fenomeni imperiali siano praticamente contemporanei e si sviluppino in due contesti molto distanti nello spazio, senza un apparente collegamento, evidenzia l'opportunità di uno studio comparativo. Ad una più attenta analisi, non si può fare a meno di notare come, in entrambi gli ambiti, il secolo immediatamente precedente sia stato caratterizzato da un momento particolarmente favorevole per la cultura – el renacimiento asturiano e the alfredian renaissance – reso possibile dall'azione attiva di due monarchi, Alfonso III di Asturia e León (866-910) e Alfred di Wessex (871-899). Nelle corti di questi sovrani vennero redatte delle cronache (le Crónicas Asturianas e la Anglo-Saxon Chronicle) nelle quali si proponeva una chiave di lettura della storia tesa a ricercare una nuova identità per i rispettivi popoli e si sottolineava il ruolo centrale delle rispettive dinastie regnanti. L'obiettivo della tesi è pertanto duplice: da una parte si desidera comprendere in quale modo e in quale senso sia stato utilizzato il termine imperator nella documentazione presa in esame, dall'altra si prova a capire quale peso ebbero le nuove identità etniche, religiose e territoriali, elaborate nelle già citate cronache, all'interno di questi fenomeni imperiali. Per una miglior resa dell'argomentazione si è deciso di dividere la tesi in due blocchi, il primo dedicato alle cronache del IX secolo e il secondo ai documenti in cui compare il titolo imperiale, risalenti al secolo successivo. A sua volta ciascun blocco si divide quindi in due capitoli, all'interno dei quali le tematiche vengono declinate nel caso ispanico e in quello anglosassone. La tesi si apre con la presentazione dei criteri impiegati nella selezione del corpus di "documenti imperiali" (Cap. 1) – nome con cui si definiscono i diplomi al cui interno compare il titolo di imperator – che ammontano ad un totale 38, di cui 20 asturiano-leonesi (privati e pubblici) e 18 anglosassoni (esclusivamente pubblici). A seguire viene fornito il contesto storico (Cap. 2) e lo status quaestionis (Cap. 3). Nel primo capitolo del primo blocco (Cap. 4) vengono trattate le tre cronache prodotte nella corte asturiano-leonese alla fine del IX secolo: conosciute anche come Crónicas Asturianas, sono intitolate rispettivamente Crónica Albeldense, Crónica Profetica e Crónica de Alfonso III. Per rendere il quadro qui esposto il più completo possibile si inizia trattando il patrimonio librario a disposizione degli autori delle cronache. A seguire si delineano i profili delle tre opere, soffermandosi in particolar modo sulla loro paternità e datazione. Si forniscono quindi indicazioni sulla tradizione manoscritta di queste cronache per poi tracciare un percorso tra le fonti. In questa parte si chiariscono concetti come quello di identità (etnica, religiosa e geografica), e si assiste alla comparsa di temi storiografici come quelli della Reconquista e del neogoticismo. Questi elementi costituiscono il punto di partenza per un ragionamento teso a far emergere il background ideologico comune a tutte e tre cronache. Nel corrispettivo capitolo inglese (Cap. 5) si delinea un profilo della produzione letteraria, in particolare storiografica, che ha caratterizzato le ultime due decadi del IX secolo anglosassone. Si inizia inquadrando gli uomini che formarono parte della cosiddetta alfredian reinassance per poi analizzare il ruolo avuto, all'interno di questo momento di rinascita culturale, dalle traduzioni in Old English delle grandi opere storiografiche. Infine, si propone una rilettura dell'unica opera storiografica scritta ex novo – l'Anglo-Saxon Chronicle – dalla quale emerge come fil rouge il concetto di overlordship. Questo è il nome che gli studiosi moderni hanno dato all'autorità che alcuni re anglosassoni poterono esercitare al di sopra degli altri regni dell'isola: si trattava di una supremazia principalmente militare che portava un re, per periodi spesso brevi, ad imporre la propria sovranità – e talvolta dei tributi – a popolazioni diverse dalla propria. Questa idea di sovranità sovrapposta era già presente in Beda e viene recuperata dai cronisti anglosassoni che la ricollegano, in maniera evidente, alla dinastia dei re del Wessex, coniando per quei re che la detennero la parola bretwalda. A conclusione del primo blocco è presente un capitolo di confronto (Cap. 6) che permette di tirare le somme della prima metà della tesi. Si ribadiscono alcuni punti in comune tra i due casi di studio qui definiti "macrocongruenze": sia la Britannia che la Spania erano parte dell'impero romano, ma non di quello carolingio e subirono un'invasione durante l'Alto Medioevo (danesi/norvegesi la prima e islamici la seconda); in entrambi i casi la produzione di cultura scritta durante il IX secolo orbitava attorno alla figura del monarca; le cronache del periodo celebrano la dinastia regnante come elemento cardine della storia "nazionale" e così facendo ne legittimano l'autorità; fra le pagine di queste cronache vengono proposte nuove identità per entrambe le popolazioni. Tuttavia, al di là di queste evidenti somiglianze, si è notato come, all'interno della cronachistica, si sia arrivati a due modi particolari di rappresentare sé stessi, il proprio regno, il proprio popolo e il proprio contesto geografico. Sono queste differenze a suscitare un particolare interesse dal momento che, come è stato chiaro sin dalla sua fase embrionale, in nessun modo lo scopo di questa ricerca è l'omologazione: non si sta cercando di uniformare la storia inglese del IX e X secolo con quella spagnola dello stesso periodo, per quanto esse abbiano sicuramente dei punti in comune. Nel capitolo di confronto si riflette quindi sulle particolari soluzioni autorappresentative soluzioni a cui sono giunti i cronisti asturiani e anglosassoni riguardo a tre punti chiave: il recupero del passato, la concezione territoriale dell'ambiente geografico e la questione identitaria. Non si può infatti trascurare il differente peso che ebbero nei relativi ambiti il ricordo del regno visigoto e quello dell'Eptarchia anglosassone e dunque, rispettivamente, le opere di Isidoro di Siviglia e Beda il Venerabile. Sarebbe inoltre sbagliato non sottolineare le differenze tra le due nuove proposte identitarie: quella inglese su base spiccatamente etnica (Angelcynn) e quella ispanica su base principalmente religiosa (regnum Xristianorum). Non poteva infine mancare un paragrafo dedicato ai differenti rapporti tra i due ambiti studiati e il mondo carolingio contemporaneo. Nel secondo blocco vengono sviscerati i fenomeni imperiali. Il capitolo dedicato all'ambito ispanico (Cap. 7) si apre con una riflessione sulle varie figure di scriptores del regno di León e sul peso avuto dai formulari visigoti nella documentazione altomedievale. Al principio del corrispettivo capitolo inglese (Cap. 8) vengono invece presentati due casi di utilizzo del termine imperiale precedenti il X secolo: quello di sant'Oswald di Northumbria (634-642) nella Vita Sancti Columbae di Adomnano di Iona e quello di Coenwulf di Mercia (796-821) nel documento S153. Seguono due paragrafi dedicati alla documentazione di Edward the Elder (899-924) e Æthelstan (924-939) che mettono in luce un sostanziale sviluppo della titolatura regia, indice di un progressivo ampliamento dell'autorità di questi monarchi. Il centro di entrambi i capitoli del secondo blocco consiste nella dettagliata analisi dei documenti imperiali e nelle riflessioni che da questa scaturiscono. Nel caso spagnolo è possibile affermare con una certa sicurezza che l'uso del titolo imperator ebbe inizio con il figlio, Ordoño II, che lo attribuì al padre per rafforzare la propria posizione di re di León. Tra la morte di Ordoño II (924) e l'ascesa al trono di Ramiro II (931) il titolo cominciò ad essere adoperato anche nella documentazione privata, senza per questo scomparire da quella regia. Non è purtroppo possibile cercare di ricondurre il fenomeno imperiale ispanico alla figura di uno scriptor in particolare – a differenza del caso inglese –; va però fatto presente che alcuni testi risalenti alla seconda metà del secolo differiscono dai documenti di Ordoño II nell'impiego del termine, poiché questo viene usato in riferimento al re vivente, anziché al padre defunto. Il titolo, almeno all'inizio del X secolo, non sembra riflettere un'autorità superiore (per l'appunto imperiale), ma richiama la sua più antica accezione, quella di "generale vittorioso" e costituisce una prerogativa dei sovrani leonesi. Per quanto riguarda il fenomeno imperiale inglese, invece, è possibile individuare un punto di inizio nei famosi alliterative charters, probabilmente redatti da Koenwald di Worcester (928/9- 957), sulla cui paternità si discute lungamente nella tesi. Sembra chiaro che imperator altro non sia che la traduzione latina di quello che gli storici hanno definito overlord. Tramite l'impiego di tale titolo i sovrani anglosassoni hanno voluto rappresentare la loro crescente egemonia sugli altri regni dell'isola, rivendicando così un'autorità più territoriale che etnica. Occorre però far presente che l'uso della terminologia imperiale forma parte di quel più ampio processo di evoluzione della titolatura regia già iniziato con Edward the Elder. Queste riflessioni vengono poi messe in relazione con quelle del primo blocco e sviluppate nelle conclusioni (Cap. 9). Esse vertono su quattro punti fondamentali: l'uso del documento e della lingua latina nei due ambiti; la Britannia e la Spania come universi a sé; il significato di imperator nei due contesti documentari; la concezione territoriale come presupposto teorico e geografico di questo utilizzo. La lettura delle fonti ci permette di affermare che entrambi i contesti rappresentavano per i rispettivi sovrani degli universi idealmente a sé stanti. I sovrani leonesi e anglosassoni ereditarono dai loro predecessori non solo una "missione" politica – di riconquista per i primi e di controllo per i secondi –, ma anche una specifica concezione – diversa per ciascun caso – dell'ambiente geografico in cui si trovavano a operare. La Britannia del re-imperatore anglosassone è la Britannia di Beda, frammentata e divisa, eppure tutto sommato unita. La Spania dei re leonesi è la Spania di Isidoro, unita, omogenea, ma drammaticamente perduta. Tuttavia, per il caso spagnolo e nel periodo qui preso in esame, al titolo non venne mai accostato un riferimento spaziale che rimandasse ad un dominio su tutta la penisola. In quello inglese, invece, tale accostamento ci fu, ma il riferimento geografico alla Britannia non fu un'esclusiva del titolo imperiale. Possiamo quindi dire che, nel caso inglese, il titolo nacque per il bisogno di tradurre in latino un'autorità indiretta ed egemonica (come quella di un rex regum), e perse poi questo significato – e quindi l'uso –, quando la situazione politica del regno si modificò; nel caso spagnolo invece, avvenne un'elaborazione quasi simmetricamente opposta. Il titolo, inizialmente usato nel suo significato più antico di "generale vittorioso" o "signore potente", venne poi reinterpretato quando nell'XI e XII secolo cambiarono gli equilibri politici della penisola. In questo periodo troviamo infatti sovrani come Alfonso VI e Alfonso VII impiegare titolature quali imperator totius Hispaniae. In entrambi i casi, l'imperator venne inteso come sinonimo di rex regum, ma in due momenti diversi: ovvero quando ve ne fu effettivamente bisogno. La tesi è provvista di mappe e della bibliografia, divisa tra fonti e studi. Inoltre si è considerato utile aggiungere in appendice i testi dei documenti imperiali. ; The subject of this thesis is the peculiar presence of the term imperator in a small, but still significant, number of 10th century documents from the reign of Asturia and León and from Britain. The fact that these two "imperial phenomena" coexisted and developed in two very distant contexts, without an apparent connection, makes a comparative study necessary. Also, in both areas the previous century was characterized by a particularly favorable moment for culture - el renacimiento asturiano and the alfredian renaissance - made possible by the action of two monarchs, Alfonso III of Asturia and León (866-910) and Alfred of Wessex (871-899). In these sovereigns' courts, chronicles were drawn up (the Crónicas Asturianas and the Anglo-Saxon Chronicle), proposing an interpretation of history which tend to seek a new identity for the respective peoples, highlighting the central role of the respective ruling dynasties. The aim of the thesis is therefore twofold: on the one hand, to understand in what way and in what sense the term imperator was used in the documentation examined; on the other hand, to estimate what weight the new ethnic, religious and territorial identities had within these imperial phenomena. For a better performance of the argument, it was decided to divide the thesis into two parts, the first dedicated to the chronicles of the 9th century and the second to the documents of the following century in which the imperial title appears. In turn, each part is divided into two chapters focused on Hispanic and Anglo-Saxon cases. The thesis opens with the presentation of the criteria used in the selection of the corpus (Ch. 1), which amounts to a total of 38 imperial documents, of which 20 Asturian-Leonese (private and public) and 18 Anglo-Saxon (exclusively public). The historical context (Ch. 2) and the status quaestionis (Ch. 3) are provided below. The first chapter of the first part (Ch. 4) deals with the three chronicles produced in the Asturian-Leonese court at the end of the 9th century. Also known as Crónicas Asturianas. they are respectively entitled Crónica Albeldense, Crónica Profetica and Crónica de Alfonso III. This chapter starts treating the Asturian library, available to the authors of the chronicles, and follows with the description of each chronicle, focusing on their paternity and dating. It then provides information about the manuscript tradition of each chronicle and it finally ends with an overall reading of the sources. Here, concepts such as identity (ethnic, religious and geographic) are clarified, and we observe the origin of historiographic themes such as those of the Reconquista and neo-Gothicism. These elements constitute the starting point for a reflection aimed at bringing out the ideological background common to all three chronicles. In the corresponding English chapter (Ch. 5) is outlined a profile of the literary production, in particular historiographic, which characterized the last two decades of the 9th century in England. We start by framing the men who formed part in the so-called alfredian reinassance and then analyze the role played in this moment of cultural rebirth by the translations in Old English of the great historiographic works. Finally, we propose a rereading of the only historiographic work written ex novo, the Anglo-Saxon Chronicle, where the concept of overlordship emerges as a common thread. Overlordship is the name that modern scholars have given to the authority that some Anglo-Saxon kings were able to exercise over other kings in the island. It is a predominantly military supremacy which leads a king, for often short periods, to impose his sovereignty - and sometimes tributes - on populations other than his own. This idea of overlapped sovereignty was already present in Beda and is recovered by the Anglo-Saxon chroniclers who relate it, explicity, to the dynasty of the kings of Wessex, coining for those kings who held it the term bretwalda. At the end of the first part there is a comparison chapter (Ch. 6) that draws the conclusions of the first half of the thesis. Some points in common (here called "macrocongruenze") between the two case studies are reiterated: both Britain and Spania formed part of the Roman Empire, but not of the Carolingian Empire and both suffered an invasion during the Early Middle Ages (Danes / Norwegians and Muslims); in both cases the production of written culture, during the 9th century, orbited around the figure of the monarch; the chronicles celebrate the reigning dynasty as the centre of "national" history to legitimize its authority; among the pages of these chronicles new identities are proposed for both populations. However, beyond these obvious similarities, it has been noted that the chronicles adopted two different ways of self-representing themselves, their kingdom, their people and their geographical context. The comparison chapter therefore reflects on three key points: the recovery of the past, the territorial conception of the geographical environment and the identity issue. In fact, we cannot neglect the different importance that the memory of the Visigoth kingdom and of the Anglo-Saxon Heptarchy (and therefore, respectively, the works of Isidore of Seville and the Venerable Bede) had. It would also be wrong not to underline the differences between the two new identity proposals: the English one had a distinctly ethnic base (Angelcynn), while the Hispanic base was mainly religious base (regnum Xristianorum). The last paragraph if finally dedicated to the different relationships between the two areas studied and the contemporary Carolingian world could not be missing. In the second block imperial phenomena are examined. The chapter dedicated to the Hispanic context (Ch. 7) opens with a reflection on the various figures of scriptores of the kingdom of León and on the weight of Visigoth formulae in the early medieval documentation. At the beginning of the corresponding English chapter (Ch. 8) are presented two cases of a use of the imperial term preceding the 10th century: that of Saint Oswald of Northumbria (634-642) in the Adomnan of Hy's Vita Sancti Columbae of and that of Coenwulf of Mercia in the charter S153. These cases are followed by two paragraphs dedicated to Edward the Elder's and Æthelstan's documentation, which highlight a substantial development of the royal title, pointing out an expansion of the authority of these monarchs. The center of both the chapters of the second block consists in the detailed analysis of the imperial documents and in the reflections that arise from it. In the Spanish case, it is possible to affirm with some certainty that the use of the imperator title began with his son, Ordoño II, who attributed it to his father to strengthen his position as king of León. Between the death of Ordoño II (924) and the ascent to the throne of Ramiro II (931), the title also began to be employed into private documentation, without disappearing in the public one. Unfortunately, it is not possible, as it is in the English case, to trace the Hispanic imperial phenomenon back to a particular scriptor. However, it should be noted that some texts dating from the second half of the century differ from the charters of Ordoño II in the use of the term, adopting it in reference to the living king, rather than the deceased father. The title, at least at the beginning of the tenth century, does not seem to reflect a superior (or imperial) authority, but recalls its most ancient meaning, of "victorious general" and constitutes a prerogative of the Leonese sovereigns. As for the English imperial phenomenon, however, it is possible to identify a starting point in the famous alliterative charters, probably drawn up by Koenwald of Worcester (928/9- 957), whose authorship is largely discussed in the thesis. It seems clear that imperator is nothing but the Latin translation of what historians have called overlord. Through the use of this title, the Anglo-Saxon rulers wanted to represent their growing hegemony over the other kingdoms of the island, thus claiming a more territorial than ethnic authority. However, it should be noted that the use of imperial terminology forms part of the broader process of evolution of the royal title that started with Edward the Elder. These reflections are then related to those of the first part and developed in the conclusions (Ch. 9). They focus on four fundamental points: the use of the documentation and the Latin language in the two areas; Britain and Spania as self-contained universes; the meaning of imperator in the two documentary contexts; the territorial conception as a theoretical and geographical assumption of this use. Reading the sources allows us to affirm that both contexts represented universes ideally self-contained for their respective sovereigns. The Leonese and Anglo-Saxon rulers inherited from their predecessors not only a political "mission" - reconquering for the former and control for the latter -, but also a specific conception - different for each case - of the geographical environment in which they found themselves operate. The Britannia of the Anglo-Saxon king-emperor is Bede's Britannia, fragmented and divided, but spiritually united. The Spania of the Leonese kings is Isidoro's Spania, united, homogeneous, but dramatically lost. However, for the Spanish case in the period examined here, the imperial title was never related to a geographical reference; in the English one, the geographical reference to Britannia existed, but was not exclusive to the imperial title. We can therefore say that, in the English case, the title was born out of the need to translate into Latin an indirect and hegemonic authority (like that of a rex regum), and then lost this meaning - and therefore the use - when the political situation of the kingdom changed. In the Spanish case, conversely, an almost symmetrically opposite processing took place. The title, initially used in its oldest meaning as "victorious general" or "powerful lord", was reinterpreted in the 11th and 12th centuries, when the political balance of the peninsula changed. In this period, we find in fact rulers like Alfonso VI and Alfonso VII employing titles such as imperator totius Hispaniae. In both cases, the emperor was intended as a synonym for rex regum, but in two different moments - always when it was more needed. The thesis is equipped with maps and bibliography, divided between sources and studies. Furthermore, it was considered useful to add a final appendix with the texts of the imperial documents. ; El tema de esta tesis es la aparición peculiar del término imperator en un número pequeño, pero significativo, de documentos del siglo X procedentes de los reinos de Asturias y León y de Inglaterra. Si en sí mismo este tipo de "coincidencia histórica" capta la atención, el hecho de que los dos fenómenos imperiales sean prácticamente contemporáneos y se desarrollen en dos contextos muy distantes en el espacio, sin una conexión aparente, pone de manifiesto la necesidad de un estudio comparativo. Tras una ulterior búsqueda, no pasa desapercibido cómo, en ambas áreas, el siglo inmediatamente anterior se caracterizó por ser un momento particularmente favorable para la cultura – el renacimiento asturiano y the alfredian reinassence –, hecho posible por la acción de dos monarcas, Alfonso III de Asturias y León (866-910) y Alfred de Wessex (871-899). En los entornos de estos soberanos, se elaboraron crónicas (las Crónicas Asturianas y la Anglo-Saxon Chronicle) que proponían una lectura de la historia destinada a buscar una nueva identidad para los respectivos pueblos, subrayando el papel central de las respectivas dinastías gobernantes. El objetivo de la tesis es, por lo tanto, doble: por un lado, se quiere entender de qué manera y en qué sentido se utilizó el término imperator en la documentación examinada y, por otro lado, tratamos de comprender qué peso tenían las nuevas identidades étnicas, religiosas y territoriales, dentro de estos fenómenos imperiales. Para una mejor presentación de los argumentos, se decidió dividir la tesis en dos bloques: el primero dedicado a las crónicas del siglo IX y el segundo a los documentos del siglo siguiente en los que aparece el título imperial. A su vez, cada bloque se divide en dos capítulos donde se desarrollan las temáticas en los casos hispanos y anglosajones. La tesis comienza con la presentación de los criterios utilizados para la selección del corpus de "documentos imperiales" (Capítulo 1) – los diplomas donde aparece el título de imperator –, que asciende a un total de treinta y ocho, veinte de los cuales son asturianos-leoneses (privados y públicos) y dieciocho anglosajones (exclusivamente públicos). El contexto histórico (Capítulo 2) y el status quaestionis (Capítulo 3) se proporcionan a continuación. En el primer capítulo del primer bloque (Capítulo 4) se presentan las tres crónicas producidas en la corte asturiano-leonesa a finales del siglo IX. También conocidas como Crónicas Asturianas, estas son la Crónica Albeldense, la Crónica Profética y la Crónica de Alfonso III. Para conseguir una visión lo más completa posible, comenzamos viendo los libros que los autores de las crónicas tenían a su disposición. A continuación, se analizan las tres obras, con una particular atención a su autoría y datación. Finalmente, proporcionamos indicaciones sobre la tradición manuscrita de estas crónicas y trazamos un camino entre las fuentes. En esta parte se van perfilando cuestiones cruciales, como la identidad (étnica, religiosa y geográfica), y temas historiográficos, como la Reconquista y el neogoticismo. Estos elementos constituyen el punto de partida para un razonamiento destinado a resaltar el trasfondo ideológico común a las tres crónicas. En el capítulo sucesivo (Capítulo 5) se traza un perfil de la producción literaria, en particular historiográfica, que caracterizó las últimas dos décadas del siglo IX anglosajón. Se comienza enmarcando a los hombres que formaron parte del llamado alfredian reinassance y analizando sucesivamente el papel desempeñado por las traducciones en Old English de las grandes obras historiográficas en este momento de renacimiento cultural. Finalmente, proponemos una nueva lectura de la única obra historiográfica escrita desde cero, la Anglo-Saxon Chronicle, a partir de la cual el concepto de overlordship emerge como un hilo conductor. Este es el nombre que los eruditos modernos le han dado a la autoridad que algunos reyes anglosajones pudieron ejercer sobre los otros reyes de la isla. Es una supremacía predominantemente militar que lleva a un rey – a menudo por períodos cortos – a imponer su soberanía, y a veces tributos, a poblaciones distintas de la suya. Esta idea de soberanía superpuesta ya estaba presente en Beda y es recuperada por los cronistas anglosajones que la relacionan, evidentemente, con la dinastía de los reyes de Wessex, acuñando para aquellos reyes la palabra bretwalda. Al final del primer bloque hay un capítulo de comparación (Capítulo 6) que permite resumir las conclusiones de la primera mitad de la tesis. Se reiteran algunos puntos en común entre los dos estudios del caso: tanto Britannia como Spania formaron parte del Imperio Romano, pero no del Imperio Carolingio y sufrieron una invasión durante la Alta Edad Media (Daneses / Noruegos e islámicos); en ambos casos, la producción de cultura escrita durante el siglo IX orbitaba alrededor de la figura del monarca. Las crónicas resultantes de este período celebran la dinastía reinante como la piedra angular de la historia "nacional" y al hacerlo legitiman su autoridad; entre las páginas de estas crónicas se proponen nuevas identidades para ambas poblaciones. Sin embargo, más allá de estas similitudes obvias, se ha observado que dentro de las crónicas ha habido dos formas particulares de representación de sí mismos, de su reino, de su gente y de su contexto geográfico. Son estas diferencias las que despiertan un interés particular, ya que, como ha quedado claro desde el principio, no hay absolutamente ningún intento de homologar la historia inglesa de los siglos IX y X con la historia española del mismo período, aunque sin duda tienen puntos en común. Por lo tanto, el capítulo de comparación reflexiona sobre las particulares formas de auto-representación proporcionadas por los cronistas asturianos y anglosajones y se centra en tres puntos clave: la recuperación del pasado, la concepción territorial del entorno geográfico y la cuestión relativa a la identidad. De hecho, no podemos descuidar el peso diferente que tuvo el recuerdo del reino visigodo y el de la Heptarquía anglosajona y, por lo tanto, respectivamente, las obras de Isidoro de Sevilla y de Beda la Venerable. También sería un error no subrayar las diferencias entre las dos nuevas propuestas de identidad: la inglesa, con una base claramente étnica (Angelcynn) y la hispana, con una base principalmente religiosa (regnum Xristianorum). Finalmente, no podía faltar un párrafo dedicado a las diferentes relaciones entre las dos áreas estudiadas y el mundo carolingio contemporáneo. En el segundo bloque se examinan los fenómenos imperiales. El capítulo dedicado al contexto hispano (Capítulo 7) comienza con una reflexión sobre las diversas figuras de los scriptores del reino de León y sobre el peso de las fórmulas visigodas en la documentación altomedieval. Al comienzo del capítulo correspondiente en inglés (Capítulo 8) se presentan dos casos de uso del término imperial anterior al siglo X: el de San Oswald de Northumbria (634-642) en la Vita Sancti Columbae de Adomnano de Iona y el de Coenwulf de Mercia (796-821) en el documento S153. Siguen dos párrafos dedicados a la documentación de Edward the Elder (899-924) y Æthelstan (924-939), donde se destaca un desarrollo sustancial del título real que indica una expansión de la autoridad insular de estos monarcas. El centro de ambos capítulos del segundo bloque consiste en el análisis detallado de los documentos imperiales y en las reflexiones que surgen de esto. En el caso español se puede concluir que, aunque hay rastros de un empleo del título imperial en la documentación de Alfonso III, es posible afirmar con cierta certeza que el uso del título imperator comenzó con su hijo, Ordoño II (914-924), quien lo atribuyó a su padre para fortalecer su posición como rey de León. Entre la muerte de Ordoño II (924) y el ascenso al trono de Ramiro II (931), el título también pasó a la documentación privada, sin desaparecer de la pública. Desafortunadamente, no es posible, como en el caso inglés, tratar de rastrear el fenómeno imperial hispano hasta la figura de un escritor en particular. Sin embargo, debe tenerse en cuenta que algunos textos que datan de la segunda mitad del siglo difieren de los documentos de Ordoño II en el uso del término, ya que se emplea en referencia al rey vivo y no al padre fallecido. El título, al menos a principios del siglo X, no parece reflejar una autoridad superior (precisamente imperial), pero recuerda su significado más antiguo, el de "general victorioso" y constituye una prerrogativa de los soberanos leoneses. En cuanto al fenómeno imperial inglés, por otro lado, es posible identificar un punto de partida en los famosos alliterative charters, probablemente producidos por Koenwald de Worcester (928/9- 957), cuya autoría se discute extensamente en la tesis. Parece que imperator no es más que la traducción latina de lo que los historiadores han llamado overlord. Mediante el uso de este título, los gobernantes anglosajones querían representar su creciente hegemonía sobre los otros reinos de la isla, reclamando así una autoridad más territorial que étnica. Sin embargo, debe tenerse en cuenta que el uso de la terminología imperial forma parte de ese proceso más amplio de evolución del título real que ya comenzó con Edward the Elder. En las conclusiones (Capítulo 9) se relacionan estas reflexiones con las del primer bloque desarrollándolas. Se centran en cuatro puntos fundamentales: el papel del documento y del idioma latino en las dos áreas; Britannia y Spania como universos en sí mismos; el significado de imperator en los dos contextos documentales y, por último, la concepción territorial como una premisa teórica y geográfica de este empleo de la terminología imperial. Tras leer las fuentes podemos afirmar que ambos contextos representaban, a los ojos de sus respectivos soberanos, universos dentro del universo. Los gobernantes leoneses y anglosajones heredaron de sus predecesores no solo una "misión" política – de reconquista para los primeros y de control para los segundos – sino también una concepción específica, diferente para cada caso, del entorno geográfico en el que se encontraban. La Britannia del rey-emperador anglosajón es la Britannia de Beda, fragmentada, dividida y, sin embargo, unida. La Spania de los reyes leoneses es la Spania de Isidoro, unida, homogénea, pero dramáticamente perdida. Sin embargo, para el caso español, en el período examinado aquí, nunca se encuentra el título imperial en relación a una referencia territorial que evoque un dominio sobre toda la península. En el inglés, sin embargo, existía este uso, pero la referencia geográfica a Britannia no era exclusiva del título imperial. Por lo tanto, podemos decir que, en el caso inglés, el título nació de la necesidad de traducir al latín una autoridad indirecta y hegemónica (como la de un rex regum), y luego perdió este significado – y su uso – cuando la situación política del reino cambió. En el caso español, sin embargo, tuvo lugar un procesamiento casi simétricamente opuesto. El título, utilizado inicialmente en su significado más antiguo como "general victorioso" o "señor poderoso", fue reinterpretado más tarde cuando el equilibrio político de la península cambió en los siglos XI y XII. En este período encontramos, de hecho, gobernantes como Alfonso VI y Alfonso VII que emplean títulos como imperator totius Hispaniae. En ambos casos, imperator fue concebido como sinónimo de rex regum, pero en dos momentos diferentes; cuando realmente se necesitaba. La tesis está provista de mapas y bibliografía, dividida entre fuentes y estudios. Además, se consideró útil agregar los textos de los documentos imperiales al apéndice.
Publisher's version (útgefin grein). ; Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis. ; The authors in this manuscript were working on behalf of BCAC, CCFR, CIMBA, CORECT, GECCO, OCAC, PRACTICAL, CRUK, BPC3, CAPS, PEGASUS, TRICL-ILCCO, ABCTB, APCB, BCFR, CONSIT TEAM, EMBRACE, GC-HBOC, GEMO, HEBON, kConFab/AOCS Mod SQuaD, and SWE-BRCA. The breast cancer genome-wide association analyses: BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST, respectively), and by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l'Économie, Science et Innovation du Québec through Genome Québec and the PSR-SIIRI-701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112—the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia), and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) is generously supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The ACP study is funded by the Breast Cancer Research Trust, UK. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia and acknowledges funding from the National Breast Cancer Foundation (JS). For the BCFR-NY, BCFR-PA, and BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. For BIGGS, ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. BOCS is supported by funds from Cancer Research UK (C8620/A8372/A15106) and the Institute of Cancer Research (UK). BOCS acknowledges NHS funding to the Royal Marsden/Institute of Cancer Research NIHR Specialist Cancer Biomedical Research Centre. The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CAMA study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) (SALUD-2002-C01-7462). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario (PI11/00923 and PI12/00070). COLBCCC is supported by the German Cancer Research Center (DKFZ), Heidelberg, Germany. D.T. was in part supported by a postdoctoral fellowship from the Alexander von Humboldt Foundation. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. H.A.C eceives support from the Lon V Smith Foundation (LVS39420). The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, and 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). GLACIER was supported by Breast Cancer Now, CRUK and Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf-Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HERPACC was supported by MEXT Kakenhi (No. 170150181 and 26253041) from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan, by National Cancer Center Research and Development Fund, and "Practical Research for Innovative Cancer Control (15ck0106177h0001)" from Japan Agency for Medical Research and development, AMED, and Cancer Bio Bank Aichi. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014, and 17-44-020498. ICICLE was supported by Breast Cancer Now, CRUK, and Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (A.L.F.) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (E.V.O.) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). G.C.-T. and P.W. are supported by the NHMRC. RB was a Cancer Institute NSW Clinical Research Fellow. The KOHBRA study was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 1020350; 1420190). LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. L.M.B.C. is supported by the 'Stichting tegen Kanker'. D.L. is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov" and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 × 1000"). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839, and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286, and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. MYBRCA is funded by research grants from the Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Malaysia. MYMAMMO is supported by research grants from Yayasan Sime Darby LPGA Tournament and Malaysian Ministry of Higher Education (RP046B-15HTM). The NBCS has been supported by the Research Council of Norway grant 193387/V50 (to A.-L. Børresen-Dale and V.N. Kristensen) and grant 193387/H10 (to A.-L. Børresen-Dale and V.N. Kristensen), South Eastern Norway Health Authority (grant 39346 to A.-L. Børresen-Dale and 27208 to V.N. Kristensen) and the Norwegian Cancer Society (to A.-L. Børresen-Dale and 419616 - 71248 - PR-2006-0282 to V.N. Kristensen). It has received funding from the K.G. Jebsen Centre for Breast Cancer Research (2012-2015). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, and U01 CA179715), and the North Carolina University Cancer Research Fund. The NGOBCS was supported by Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scientific Research on Priority Areas, 17015049 and for Scientific Research on Innovative Areas, 221S0001, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation, and the special Governmental EVO funds for Oulu University Hospital-based research activities. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956, and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, UMCA182910, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scientific development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network U19 CA148065. The SBCS was supported by Sheffield Experimental Cancer Medicine Centre and Breast Cancer Now Tissue Bank. The SCCS is supported by a grant from the National Institutes of Health (R01 CA092447). Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health, Office of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR 72205. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347). SGBCC is funded by the NUS start-up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/1/21/19/425. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The TBCS was funded by The National Cancer Institute, Thailand. The TNBCC was supported by a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The US3SS study was supported by Massachusetts (K.M.E., R01CA47305), Wisconsin (P.A.N., R01 CA47147) and New Hampshire (L.T.-E., R01CA69664) centers, and Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WAABCS study was supported by grants from the National Cancer Institute of the National Institutes of Health (R01 CA89085 and P50 CA125183 and the D43 TW009112 grant), Susan G. Komen (SAC110026), the Dr. Ralph and Marian Falk Medical Research Trust, and the Avon Foundation for Women. The WHI program is funded by the National Heart, Lung, and Blood Institute, the US National Institutes of Health and the US Department of Health and Human Services (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). This work was also funded by NCI U19 CA148065-01. D.G.E. is supported by the all Manchester NIHR Biomedical research center Manchester (IS-BRC-1215-20007). HUNBOCS, Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grant KTIA-OTKA CK-80745, NKFI_OTKA K-112228. C.I. received support from the Nontherapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI P30-CA-51008) and the Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research. K.M. is supported by CRUK C18281/A19169. City of Hope Clinical Cancer Community Research Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J Weitzel) from the National Cancer Institute and the office of the Directory, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The colorectal cancer genome-wide association analyses: Colorectal Transdisciplinary Study (CORECT): The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CORECT Consortium, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CORECT Consortium. We are incredibly grateful for the contributions of Dr. Brian Henderson and Dr. Roger Green over the course of this study and acknowledge them in memoriam. We are also grateful for support from Daniel and Maryann Fong. ColoCare: we thank the many investigators and staff who made this research possible in ColoCare Seattle and ColoCare Heidelberg. ColoCare was initiated and developed at the Fred Hutchinson Cancer Research Center by Drs. Ulrich and Grady. CCFR: the Colon CFR graciously thanks the generous contributions of their study participants, dedication of study staff, and financial support from the U.S. National Cancer Institute, without which this important registry would not exist. Galeon: GALEON wishes to thank the Department of Surgery of University Hospital of Santiago (CHUS), Sara Miranda Ponte, Carmen M Redondo, and the staff of the Department of Pathology and Biobank of CHUS, Instituto de Investigación Sanitaria de Santiago (IDIS), Instituto de Investigación Sanitaria Galicia Sur (IISGS), SERGAS, Vigo, Spain, and Programa Grupos Emergentes, Cancer Genetics Unit, CHUVI Vigo Hospital, Instituto de Salud Carlos III, Spain. MCCS: this study was made possible by the contribution of many people, including the original investigators and the diligent team who recruited participants and continue to work on follow-up. We would also like to express our gratitude to the many thousands of Melbourne residents who took part in the study and provided blood samples. SEARCH: We acknowledge the contributions of Mitul Shah, Val Rhenius, Sue Irvine, Craig Luccarini, Patricia Harrington, Don Conroy, Rebecca Mayes, and Caroline Baynes. The Swedish low-risk colorectal cancer study: we thank Berith Wejderot and the Swedish low-risk colorectal cancer study group. Genetics & Epidemiology of Colorectal Cancer Consortium (GECCO): we thank all those at the GECCO Coordinating Center for helping bring together the data and people that made this project possible. ASTERISK: we are very grateful to Dr. Bruno Buecher without whom this project would not have existed. We also thank all those who agreed to participate in this study, including the patients and the healthy control persons, as well as all the physicians, technicians and students. DACHS: we thank all participants and cooperating clinicians, and Ute Handte-Daub, Renate Hettler-Jensen, Utz Benscheid, Muhabbet Celik, and Ursula Eilber for excellent technical assistance. HPFS, NHS and PHS: we acknowledge Patrice Soule and Hardeep Ranu of the Dana-Farber Harvard Cancer Center High-Throughput Polymorphism Core who assisted in the genotyping for NHS, HPFS, and PHS under the supervision of Dr. Immaculata Devivo and Dr. David Hunter, Qin (Carolyn) Guo, and Lixue Zhu who assisted in programming for NHS and HPFS and Haiyan Zhang who assisted in programming for the PHS. We thank the participants and staff of the Nurses' Health Study and the Health Professionals Follow-Up Study, for their valuable contributions as well as the following state cancer registries for their help: A.L., A.Z., A.R., C.A., C.O., C.T., D.E., F.L., G.A., I.D., I.L., I.N., I.A., K.Y., L.A., M.E., M.D., M.A., M.I., N.E., N.H., N.J., N.Y., N.C., N.D., O.H., O.K., O.R., P.A., R.I., S.C., T.N., T.X., V.A., W.A., W.Y. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. We assume full responsibility for analyses and interpretation of these data. PLCO: we thank Drs. Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff or the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information Management Services Inc., Ms. Barbara O'Brien and staff, Westat Inc. and Drs. Bill Kopp, Wen Shao and staff, SAIC-Frederick. Most importantly, we acknowledge the study participants for their contributions for making this study possible. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by NCI. PMH: we thank the study participants and staff of the Hormones and Colon Cancer study. WHI: we thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at https://cleo.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short20List.pdf. CORECT: The CORECT Study was supported by the National Cancer Institute, National Institutes of Health (NCI/NIH), U.S. Department of Health and Human Services (grant numbers U19 CA148107, R01 CA81488, P30 CA014089, R01 CA197350; P01 CA196569; and R01 CA201407) and National Institutes of Environmental Health Sciences, National Institutes of Health (grant number T32 ES013678). The ATBC Study was supported by the US Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C) from the National Cancer Institute. The Cancer Prevention Study-II Nutrition Cohort is funded by the American Cancer Society. ColoCare: This work was supported by the National Institutes of Health (grant numbers R01 CA189184, U01 CA206110, 2P30CA015704-40 (Gilliland)), the Matthias Lackas-Foundation, the German Consortium for Translational Cancer Research, and the EU TRANSCAN initiative. Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): funding for GECCO was provided by the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (grant numbers U01 CA137088, R01 CA059045, and U01 CA164930). This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704. The Colon Cancer Family Registry (CFR) Illumina GWAS was supported by funding from the National Cancer Institute, National Institutes of Health (grant numbers U01 CA122839, R01 CA143247). The Colon CFR/CORECT Affymetrix Axiom GWAS and OncoArray GWAS were supported by funding from National Cancer Institute, National Institutes of Health (grant number U19 CA148107 to S.G.). The Colon CFR participant recruitment and collection of data and biospecimens used in this study were supported by the National Cancer Institute, National Institutes of Health (grant number UM1 CA167551) and through cooperative agreements with the following Colon CFR centers: Australasian Colorectal Cancer Family Registry (NCI/NIH grant numbers U01 CA074778 and U01/U24 CA097735), USC Consortium Colorectal Cancer Family Registry (NCI/NIH grant numbers U01/U24 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (NCI/NIH grant number U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (NCI/NIH grant number U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (NCI/NIH grant number U01/U24 CA074794), and University of Hawaii Colorectal Cancer Family Registry (NCI/NIH grant number U01/U24 CA074806), Additional support for case ascertainment was provided from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute to Fred Hutchinson Cancer Research Center (Control Nos. N01-CN-67009 and N01-PC-35142, and Contract No. HHSN2612013000121), the Hawai'i Department of Health (Control Nos. N01-PC-67001 and N01-PC-35137, and Contract No. HHSN26120100037C, and the California Department of Public Health (contracts HHSN261201000035C awarded to the University of Southern California, and the following state cancer registries: A.Z., C.O., M.N., N.C., N.H., and by the Victoria Cancer Registry and Ontario Cancer Registry. ESTHER/VERDI was supported by grants from the Baden–Württemberg Ministry of Science, Research and Arts and the German Cancer Aid. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. GALEON: FIS Intrasalud (PI13/01136). The MCCS was further supported by Australian NHMRC grants 509348, 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. MSKCC: the work at Sloan Kettering in New York was supported by the Robert and Kate Niehaus Center for Inherited Cancer Genomics and the Romeo Milio Foundation. Moffitt: This work was supported by funding from the National Institutes of Health (grant numbers R01 CA189184, P30 CA076292), Florida Department of Health Bankhead-Coley Grant 09BN-13, and the University of South Florida Oehler Foundation. Moffitt contributions were supported in part by the Total Cancer Care Initiative, Collaborative Data Services Core, and Tissue Core at the H. Lee Moffitt Cancer Center & Research Institute, a National Cancer Institute-designated Comprehensive Cancer Center (grant number P30 CA076292). SEARCH: Cancer Research UK (C490/A16561). The Spanish study was supported by Instituto de Salud Carlos III, co-funded by FEDER funds –a way to build Europe– (grants PI14-613 and PI09-1286), Catalan Government DURSI (grant 2014SGR647), and Junta de Castilla y León (grant LE22A10-2). The Swedish Low-risk Colorectal Cancer Study: the study was supported by grants from the Swedish research council; K2015-55 × -22674-01-4, K2008-55 × -20157-03-3, K2006-72 × -20157-01-2 and the Stockholm County Council (ALF project). CIDR genotyping for the Oncoarray was conducted under contract 268201200008I (to K.D.), through grant 101HG007491-01 (to C.I.A.). The Norris Cotton Cancer Center - P30CA023108, The Quantitative Biology Research Institute - P20GM103534, and the Coordinating Center for Screen Detected Lesions - U01CA196386 also supported efforts of C.I.A. This work was also supported by the National Cancer Institute (grant numbers U01 CA1817700, R01 CA144040). ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue Régionale Contre le Cancer (LRCC). COLO2&3: National Institutes of Health (grant number R01 CA060987). DACHS: This work was supported by the German Research Council (BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, HO 5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1, and BR 1704/17-1), the Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany, and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01ER1505A, and 01ER1505B). DALS: National Institutes of Health (grant number R01 CA048998 to M.L.S). HPFS is supported by National Institutes of Health (grant numbers P01 CA055075, UM1 CA167552, R01 137178, and P50 CA127003), NHS by the National Institutes of Health (grant numbers UM1 CA186107, R01 CA137178, P01 CA087969, and P50 CA127003), NHSII by the National Institutes of Health (grant numbers R01 050385CA and UM1 CA176726), and PHS by the National Institutes of Health (grant number R01 CA042182). MEC: National Institutes of Health (grant numbers R37 CA054281, P01 CA033619, and R01 CA063464). OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (grant number U01 CA074783); see Colon CFR section above. As subset of ARCTIC, OFCCR is supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. T.J.H. and B.W.Z. are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples was genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS, Colon CGEMS pancreatic cancer scan (PanScan), and the Lung Cancer and Smoking study. The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, 23 and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH: National Institutes of Health (grant number R01 CA076366). VITAL: National Institutes of Health (grant number K05-CA154337). WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The head and neck cancer genome-wide association analyses: The study was supported by NIH/NCI: P50 CA097190, and P30 CA047904, Canadian Cancer Society Research Institute (no. 020214) and Cancer Care Ontario Research Chair to R.H. The Princess Margaret Hospital Head and Neck Cancer Translational Research Program is funded by the Wharton family, Joe's Team, Gordon Tozer, Bruce Galloway and the Elia family. Geoffrey Liu was supported by the Posluns Family Fund and the Lusi Wong Family Fund at the Princess Margaret Foundation, and the Alan B. Brown Chair in Molecular Genomics. This publication presents data from Head and Neck 5000 (H&N5000). H&N5000 was a component of independent research funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Human papillomavirus (HPV) in H&N5000 serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). National Cancer Institute (R01-CA90731); National Institute of Environmental Health Sciences (P30ES10126). The authors thank all the members of the GENCAPO team/The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). CPS-II recruitment and maintenance is supported with intramural research funding from the American Cancer Society. Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1 × 01HG007780-0. The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19-CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission's 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222). The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to S.B., and Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). We thank Leticia Fernandez, Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba and Sergio and Rosalina Koifman, for their efforts with the IARC Latin America study São Paulo center. The IARC Central Europe study was supported by European Commission's INCO-COPERNICUS Program (IC15- CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28. The IARC Oral Cancer Multicenter study was funded by grant S06 96 202489 05F02 from Europe against Cancer; grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The lung cancer genome-wide association analyses: Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by (U19-CA148127, CA148127S1, U19CA203654, and Cancer Prevention Research Institute of Texas RR170048). The ILCCO data harmonization is supported by Cancer Care Ontario Research Chair of Population Studies to R. H. and Lunenfeld-Tanenbaum Research Institute, Sinai Health System. The TRICL-ILCCO OncoArray was supported by in-kind genotyping by the Centre for Inherited Disease Research (26820120008i-0-26800068-1). The CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03-0365, and FIS-07-BI060604, FICYT/Asturias grant numbers FICYT PB02-67 and FICYT IB09-133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiologia y Salud Pública. CIBERESP, SPAIN. The work performed in the CARET study was supported by the National Institute of Health/National Cancer Institute: UM1 CA167462 (PI: Goodman), National Institute of Health UO1-CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA151989-01A1(PI Doherty). The Liverpool Lung project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578, CA074386. The Multi-ethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464, and CA148127. The work performed in MSH-PMH study was supported by The Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. NJLCS was funded by the State Key Program of National Natural Science of China (81230067), the National Key Basic Research Program Grant (2011CB503805), the Major Program of the National Natural Science Foundation of China (81390543). The Norway study was supported by Norwegian Cancer Society, Norwegian Research Council. The Shanghai Cohort Study (SCS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The Singapore Chinese Health Study (SCHS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The work in TLC study has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997), and by a Cancer Center Support Grant (CCSG) at the H. Lee Moffitt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30-CA76292). The Vanderbilt Lung Cancer Study—BioVU dataset used for the analyses described was obtained from Vanderbilt University Medical Center's BioVU, which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the Vanderbilt CTSA grant UL1TR000445 from NCATS/NIH. Dr. Aldrich was supported by NIH/National Cancer Institute K07CA172294 (PI: Aldrich) and Dr. Bush was supported by NHGRI/NIH U01HG004798 (PI: Crawford). The Copenhagen General Population Study (CGPS) was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The Kentucky Lung Cancer Research Initiative was supported by the Department of Defense [Congressionally Directed Medical Research Program, U.S. Army Medical Research and Materiel Command Program] under award number: 10153006 (W81XWH-11-1-0781). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. This research was also supported by unrestricted infrastructure funds from the UK Center for Clinical and Translational Science, NIH grant UL1TR000117 and Markey Cancer Center NCI Cancer Center Support Grant (P30 CA177558) Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics. The M.D. Anderson Cancer Center study was supported in part by grants from the NIH (P50 CA070907, R01 CA176568) (to X.W.), Cancer Prevention & Research Institute of Texas (RP130502) (to X.W.), and The University of Texas MD Anderson Cancer Center institutional support for the Center for Translational and Public Health Genomics. The deCODE study of smoking and nicotine dependence was funded in part by a grant from NIDA (R01- DA017932). The study in Lodz center was partially funded by Nofer Institute of Occupational Medicine, under task NIOM 10.13: Predictors of mortality from non-small cell lung cancer—field study. Genetic sharing analysis was funded by NIH grant CA194393. The research undertaken by M.D.T., L.V.W., and M.S.A. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.D.T. holds a Medical Research Council Senior Clinical Fellowship (G0902313). The work to assemble the FTND GWAS meta-analysis was supported by the National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA) grant number R01 DA035825 (Principal Investigator [PI]: DBH). The study populations included COGEND (dbGaP phs000092.v1.p1 and phs000404.v1.p1), COPDGene (dbGaP phs000179.v3.p2), deCODE Genetics, EAGLE (dbGaP phs000093.vs.p2), and SAGE. dbGaP phs000092.v1.p1). See Hancock et al. Transl Psychiatry 2015 (PMCID: PMC4930126) for the full listing of funding sources and other acknowledgments. The Resource for the Study of Lung Cancer Epidemiology in North Trent (ReSoLuCENT)study was funded by the Sheffield Hospitals Charity, Sheffield Experimental Cancer Medicine Centre and Weston Park Hospital Cancer Charity. The ovarian cancer genome-wide association analysis: The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The OCAC OncoArray genotyping project was funded through grants from the U.S. National Institutes of Health (CA1X01HG007491-01 (C.I.A.), U19-CA148112 (T.A.S.), R01-CA149429 (C.M.P.), and R01-CA058598 (M.T.G.); Canadian Institutes of Health Research (MOP-86727 (L.E.K.) and the Ovarian Cancer Research Fund (A.B.). The COGS project was funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175) and through a grant from the U.S. National Institutes of Health (R01-CA122443 (E.L.G)). Funding for individual studies: AAS: National Institutes of Health (RO1-CA142081); AOV: The Canadian Institutes for Health Research (MOP-86727); AUS: The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600, 400413 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania and Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182). The Australian Ovarian Cancer Study gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation; BAV: ELAN Funds of the University of Erlangen-Nuremberg; BEL: National Kankerplan; BGS: Breast Cancer Now, Institute of Cancer Research; BVU: Vanderbilt CTSA grant from the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) (ULTR000445); CAM: National Institutes of Health Research Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Cancer Centre; CHA: Innovative Research Team in University (PCSIRT) in China (IRT1076); CNI: Instituto de Salud Carlos III (PI12/01319); Ministerio de Economía y Competitividad (SAF2012); COE: Department of Defense (W81XWH-11-2-0131); CON: National Institutes of Health (R01-CA063678, R01-CA074850; and R01-CA080742); DKE: Ovarian Cancer Research Fund; DOV: National Institutes of Health R01-CA112523 and R01-CA87538; EMC: Dutch Cancer Society (EMC 2014-6699); EPC: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom); GER: German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB 9401) and the German Cancer Research Center (DKFZ); GRC: This research has been co-financed by the European Union (European Social Fund—ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)—Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund; GRR: Roswell Park Cancer Institute Alliance Foundation, P30 CA016056; HAW: U.S. National Institutes of Health (R01-CA58598, N01-CN-55424, and N01-PC-67001); HJO: Intramural funding; Rudolf-Bartling Foundation; HMO: Intramural funding; Rudolf-Bartling Foundation; HOC: Helsinki University Research Fund; HOP: Department of Defense (DAMD17-02-1-0669) and NCI (K07-CA080668, R01-CA95023, P50-CA159981 MO1-RR000056 R01-CA126841); HUO: Intramural funding; Rudolf-Bartling Foundation; JGO: JSPS KAKENHI grant; JPN: Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare; KRA: This study (Ko-EVE) was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 0920010); LAX: American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; LUN: ERC-2011-AdG 294576-risk factors cancer, Swedish Cancer Society, Swedish Research Council, Beta Kamprad Foundation; MAC: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; Fraternal Order of Eagles; MAL: Funding for this study was provided by research grant R01- CA61107 from the National Cancer Institute, Bethesda, MD, research grant 94 222 52 from the Danish Cancer Society, Copenhagen, Denmark; and the Mermaid I project; MAS: Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; MAY: National Institutes of Health (R01-CA122443, P30-CA15083, and P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; MCC: Cancer Council Victoria, National Health and Medical Research Council of Australia (NHMRC) grants number 209057, 251533, 396414, and 504715; MDA: DOD Ovarian Cancer Research Program (W81XWH-07-0449); MEC: NIH (CA54281, CA164973, CA63464); MOF: Moffitt Cancer Center, Merck Pharmaceuticals, the state of Florida, Hillsborough County, and the city of Tampa; NCO: National Institutes of Health (R01-CA76016) and the Department of Defense (DAMD17-02-1-0666); NEC: National Institutes of Health R01-CA54419 and P50-CA105009 and Department of Defense W81XWH-10-1-02802; NHS: UM1 CA186107, P01 CA87969, R01 CA49449, R01-CA67262, UM1 CA176726; NJO: National Cancer Institute (NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, and P30-CA072720) and the Cancer Institute of New Jersey; If Sara Olson and/or Irene Orlow is a co-author, please add NCI CCSG award (P30-CA008748) to the funding sources; NOR: Helse Vest, The Norwegian Cancer Society, The Research Council of Norway; NTH: Radboud University Medical Centre; OPL: National Health and Medical Research Council (NHMRC) of Australia (APP1025142) and Brisbane Women's Club; ORE: OHSU Foundation; OVA: This work was supported by Canadian Institutes of Health Research grant (MOP-86727) and by NIH/NCI 1 R01CA160669-01A1; PLC: Intramural Research Program of the National Cancer Institute; POC: Pomeranian Medical University; POL: Intramural Research Program of the National Cancer Institute; PVD: Canadian Cancer Society and Cancer Research Society GRePEC Program; RBH: National Health and Medical Research Council of Australia; RMH: Cancer Research UK, Royal Marsden Hospital; RPC: National Institute of Health (P50-CA159981, R01-CA126841); SEA: Cancer Research UK (C490/A10119 C490/A10124); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; SIS: NIH, National Institute of Environmental Health Sciences, Z01-ES044005 and Z01-ES049033; SMC: The bbSwedish Research Council-SIMPLER infrastructure; the Swedish Cancer Foundation; SON: National Health Research and Development Program, Health Canada, grant 6613-1415-53; SRO: Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589); STA: NIH grants U01 CA71966 and U01 CA69417; SWE: Swedish Cancer foundation, WeCanCureCancer and VårKampMotCancer foundation; SWH: NIH (NCI) grant R37-CA070867; TBO: National Institutes of Health (R01-CA106414-A2), American Cancer Society (CRTG-00-196-01-CCE), Department of Defense (DAMD17-98-1-8659), Celma Mastery Ovarian Cancer Foundation; TOR: NIH grants R01-CA063678 and R01 CA063682; UCI: NIH R01-CA058860 and the Lon V Smith Foundation grant LVS39420; UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure; UKO: The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre; UKR: Cancer Research UK (C490/A6187), UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; USC: P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403, and California Cancer Research Program (00-01389V-20170, 2II0200); VAN: BC Cancer Foundation, VGH & UBC Hospital Foundation; VTL: NIH K05-CA154337; WMH: National Health and Medical Research Council of Australia, Enabling Grants ID 310670 & ID 628903. Cancer Institute NSW Grants 12/RIG/1-17 & 15/RIG/1-16; WOC: National Science Centren (N N301 5645 40). The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academia Reserve. The prostate cancer genome-wide association analyses: we pay tribute to Brian Henderson, who was a driving force behind the OncoArray project, for his vision and leadership, and who sadly passed away before seeing its fruition. We also thank the individuals who participated in these studies enabling this work. The ELLIPSE/PRACTICAL (http//:practical.icr.ac.uk) prostate cancer consortium and his collaborating partners were supported by multiple funding mechanisms enabling this current work. ELLIPSE/PRACTICAL Genotyping of the OncoArray was funded by the US National Institutes of Health (NIH) (U19 CA148537 for ELucidating Loci Involved in Prostate Cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I). Additional analytical support was provided by NIH NCI U01 CA188392 (F.R.S.). Funding for the iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112; the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This work was supported by the Canadian Institutes of Health Research, European Commission's Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, C5047/A21332 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA148537-01 (the GAME-ON initiative). We also thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network UK, and The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. The Prostate Cancer Program of Cancer Council Victoria also acknowledge grant support from The National Health and Medical Research Council, Australia (126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394, and 614296), VicHealth, Cancer Council Victoria, The Prostate Cancer Foundation of Australia, The Whitten Foundation, PricewaterhouseCoopers, and Tattersall's. E.A.O., D.M.K., and E.M.K. acknowledge the Intramural Program of the National Human Genome Research Institute for their support. The BPC3 was supported by the U.S. National Institutes of Health, National Cancer Institute (cooperative agreements U01-CA98233 to D.J.H., U01-CA98710 to S.M.G., U01-CA98216 to E.R., and U01-CA98758 to B.E.H., and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics). CAPS GWAS study was supported by the Swedish Cancer Foundation (grant no 09-0677, 11-484, 12-823), the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linneus Centre (Contract ID 70867902) financed by the Swedish Research Council, Swedish Research Council (grant no K2010-70 × -20430-04-3, 2014-2269). The Hannover Prostate Cancer Study was supported by the Lower Saxonian Cancer Society. PEGASUS was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. RAPPER was supported by the NIHR Manchester Biomedical Research Center, Cancer Research UK (C147/A25254, C1094/A18504) and the EU's 7th Framework Programme Grant/Agreement no 60186. Overall: this research has been conducted using the UK Biobank Resource (application number 16549). NHS is supported by UM1 CA186107 (NHS cohort infrastructure grant), P01 CA87969, and R01 CA49449. NHSII is supported by UM1 CA176726 (NHSII cohort infrastructure grant), and R01-CA67262. A.L.K. is supported by R01 MH107649. We would like to thank the participants and staff of the NHS and NHSII for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. ; Peer Reviewed
Only Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965101/ ; Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis. ; CAC: We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians, and administrative staff who have enabled this work to be carried out. We acknowledge all contributors to the COGS and OncoArray study design, chip design, genotyping, and genotype analyses. ABCFS: Maggie Angelakos, Judi Maskiell, Gillian Dite. ABCS: Frans Hogervorst, Sten Cornelissen and Annegien Broeks. ABCTB Investigators: Rosemary Balleine, Robert Baxter, Stephen Braye, Jane Carpenter, Jane Dahlstrom, John Forbes, Soon Lee, Debbie Marsh, Adrienne Morey, Nirmala Pathmanathan, Rodney Scott, Allan Spigelman, Nicholas Wilcken, Desmond Yip. BBCS: Eileen Williams, Elaine Ryder-Mills, Kara Sargus. BCINIS: Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet. BIGGS: Niall McInerney, Gabrielle Colleran, Andrew Rowan, Angela Jones. BREOGAN: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Munoz Garzon, Alejandro Novo Dominguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Pena Fernandez, Manuel Enguix Castelo, Maria Torres, Manuel Calaza, Jose Antunez, Maximo Fraga; Joaquin Gonzalez-Carrero and the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS. BSUCH: Peter Bugert, Medical Faculty Mannheim. CCGP: Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgard Hansen, and the Danish Cancer Biobank. CNIO-BCS: Guillermo Pita, Charo Alonso, Nuria Alvarez, Pilar Zamora, and Primitiva Menendez. CPS-II: Centers for Disease Control and Prevention National Program of Cancer Registries. The National Cancer Institute Surveillance Epidemiology, and End Results program. CTS: Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart. Dennis Deapen, Rich Pinder, and Eunjung Lee, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park and Fred Schumacher. DIETCOMPLYF: charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. Participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER: Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK: NIHR for funding. GC-HBOC: Stefanie Engert, Heide Hellebrand, Sandra Krober and LIFE. Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber. GENICA: Dr. Margarete Fischer-Bosch [HB, Wing-Yee Lo], German Cancer Consortium (DKTK), and German Cancer Research Center (DKFZ) [HB], gefordert durch die Deutsche Forschungsgemeinschaft (DFG) im Rahmen der Exzellenzstrategie des Bundes und der Lander -EXC 2180 -390900677 [HB], Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, [Yon-Dschun Ko, Christian Baisch], University of Bonn, Germany [Hans-Peter Fischer], Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [UH], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bruning, Beate Pesch, Sylvia Rabstein, Anne Lotz]; University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS: Michael Bremer. HEBCS: Rainer Fagerholm, Kirsimari Aaltonen, Karl von Smitten, Irja Erkkila. HUBCS: Shamil Gantsev. KARMA and SASBAC: Swedish Medical Research Counsel. KBCP: Eija Myohanen, Helena Kemilainen. kConFab/AOCS: Eveline Niedermayr, Family Cancer Clinics and the Clinical Follow Up Study (received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)). LMBC: Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MARIE: Petra Seibold, Judith Heinz, Nadia Obi, Sabine Behrens, Ursula Eilber, Muhabbet Celik and Til Olchers. MBCSG: Paolo Radice, Jacopo Azzollini, Bernardo Bonanni, Bernard Peissel, Roberto Villa, Giulia Cagnoli, Irene Feroce, and Cogentech Cancer Genetic Test Laboratory. NBCS: Kristine K. Sahlberg (PhD), Lars Ottestad (MD), Rolf Karesen (Prof. Em.) Dr. Ellen Schlichting (MD), Marit Muri Holmen (MD), Toril Sauer (MD), Vilde Haakensen (MD), Olav Engebraten (MD), Bjorn Naume (MD), Alexander Fossa (MD), Cecile E. Kiserud (MD), Kristin V. Reinertsen (MD), Aslaug Helland (MD), Margit Riis (MD), Jurgen Geisler (MD) and OSBREAC. NHS/NHS2: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. OBCS: Arja Jukkola-Vuorinen, Mervi Grip, Saila Kauppila, Meeri Otsukka, Leena Keskitalo and Kari Mononen. OFBCR: Teresa Selander, Nayana Weerasooriya. ORIGO: E. Krol-Warmerdam, and J. Blom. PBCS: Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner. The ethical approval for the POSH study is MREC/00/6/69, UKCRN ID: 1137. Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE: Sonja Oeser and Silke Landrith. PROCAS: NIHR for funding. RBCS: Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. SBCS: Sue Higham, Helen Cramp, Dan Connley, Ian Brock, Sabapathy Balasubramanian and Malcolm W.R. Reed. We thank the SEARCH and EPIC teams. SKKDKFZS: SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS: Ewa Putresza. UCIBCS: Irene Masunaka. UKBGS: Breast Cancer Now and the Institute of Cancer Research and NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. WHI: investigators and staff for their dedication. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community ' s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 -the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. ABCFS was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009-4363; 2015-7632]. The ABCTB was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The work of the BBCC was partly funded by ELANFond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). For the BCFRNY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. For BIGGS, ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. The BREOGAN is funded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI17/00918/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI12/00070). The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPICOxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPICOxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. Prof D Gareth Evans is supported by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). The GC-HBOC is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases, project numbers 713241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 1729-06014 and 17-44-020498. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. LMBC is supported by the "Stichting tegen Kanker." The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5x1000"). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous.pngt from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was supported by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. The NBCS has received funding from the K.G. Jebsen Centre for Breast Cancer Research; the Research Council of Norway grant 193387/V50 (to A-L Borresen-Dale and V.N. Kristensen) and grant 193387/H10 (to A-L Borresen-Dale and V.N. Kristensen), South Eastern Norway Health Authority (grant 39346 to A-L Borresen-Dale) and the Norwegian Cancer Society (to A-L Borresen-Dale and V.N. Kristensen). The NC-BCFR and OFBCR were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The NCBCS was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation and the special Governmental EVO funds for Oulu University Hospital-based research activities. The ORIGO study was supported by the Dutch Cancer Society (RUL 19971505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRINL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCS was supported by Sheffield Experimental Cancer Medicine Centre and Breast Cancer Now Tissue Bank. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council (SIMPLER, VR 2017-00644). The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WHI program is funded by the National Heart, Lung, and Blood Institute, the US National Institutes of Health and the US Department of Health and Human Services (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). This work was also funded by NCI U19 CA148065-01.
Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis. ; BCAC: We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians, and administrative staff who have enabled this work to be carried out. We acknowledge all contributors to the COGS and OncoArray study design, chip design, genotyping, and genotype analyses. ABCFS: Maggie Angelakos, Judi Maskiell, Gillian Dite. ABCS: Frans Hogervorst, Sten Cornelissen and Annegien Broeks. ABCTB Investigators: Rosemary Balleine, Robert Baxter, Stephen Braye, Jane Carpenter, Jane Dahlstrom, John Forbes, Soon Lee, Debbie Marsh, Adrienne Morey, Nirmala Pathmanathan, Rodney Scott, Allan Spigelman, Nicholas Wilcken, Desmond Yip. BBCS: Eileen Williams, Elaine Ryder-Mills, Kara Sargus. BCINIS: Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet. BIGGS: Niall McInerney, Gabrielle Colleran, Andrew Rowan, Angela Jones. BREOGAN: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Munoz Garzon, Alejandro Novo Dominguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Pena Fernandez, Manuel Enguix Castelo, Maria Torres, Manuel Calaza, Jose Antunez, Maximo Fraga; Joaquin Gonzalez-Carrero and the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS. BSUCH: Peter Bugert, Medical Faculty Mannheim. CCGP: Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgard Hansen, and the Danish Cancer Biobank. CNIO-BCS: Guillermo Pita, Charo Alonso, Nuria Alvarez, Pilar Zamora, and Primitiva Menendez. CPS-II: Centers for Disease Control and Prevention National Program of Cancer Registries. The National Cancer Institute Surveillance Epidemiology, and End Results program. CTS: Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart. Dennis Deapen, Rich Pinder, and Eunjung Lee, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park and Fred Schumacher. DIETCOMPLYF: charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. Participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER: Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK: NIHR for funding. GC-HBOC: Stefanie Engert, Heide Hellebrand, Sandra Krober and LIFE. Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber. GENICA: Dr. Margarete Fischer-Bosch [HB, Wing-Yee Lo], German Cancer Consortium (DKTK), and German Cancer Research Center (DKFZ) [HB], gefordert durch die Deutsche Forschungsgemeinschaft (DFG) im Rahmen der Exzellenzstrategie des Bundes und der Lander -EXC 2180 -390900677 [HB], Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, [Yon-Dschun Ko, Christian Baisch], University of Bonn, Germany [Hans-Peter Fischer], Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [UH], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bruning, Beate Pesch, Sylvia Rabstein, Anne Lotz]; University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS: Michael Bremer. HEBCS: Rainer Fagerholm, Kirsimari Aaltonen, Karl von Smitten, Irja Erkkila. HUBCS: Shamil Gantsev. KARMA and SASBAC: Swedish Medical Research Counsel. KBCP: Eija Myohanen, Helena Kemilainen. kConFab/AOCS: Eveline Niedermayr, Family Cancer Clinics and the Clinical Follow Up Study (received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)). LMBC: Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MARIE: Petra Seibold, Judith Heinz, Nadia Obi, Sabine Behrens, Ursula Eilber, Muhabbet Celik and Til Olchers. MBCSG: Paolo Radice, Jacopo Azzollini, Bernardo Bonanni, Bernard Peissel, Roberto Villa, Giulia Cagnoli, Irene Feroce, and Cogentech Cancer Genetic Test Laboratory. NBCS: Kristine K. Sahlberg (PhD), Lars Ottestad (MD), Rolf Karesen (Prof. Em.) Dr. Ellen Schlichting (MD), Marit Muri Holmen (MD), Toril Sauer (MD), Vilde Haakensen (MD), Olav Engebraten (MD), Bjorn Naume (MD), Alexander Fossa (MD), Cecile E. Kiserud (MD), Kristin V. Reinertsen (MD), Aslaug Helland (MD), Margit Riis (MD), Jurgen Geisler (MD) and OSBREAC. NHS/NHS2: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. OBCS: Arja Jukkola-Vuorinen, Mervi Grip, Saila Kauppila, Meeri Otsukka, Leena Keskitalo and Kari Mononen. OFBCR: Teresa Selander, Nayana Weerasooriya. ORIGO: E. Krol-Warmerdam, and J. Blom. PBCS: Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner. The ethical approval for the POSH study is MREC/00/6/69, UKCRN ID: 1137. Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE: Sonja Oeser and Silke Landrith. PROCAS: NIHR for funding. RBCS: Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. SBCS: Sue Higham, Helen Cramp, Dan Connley, Ian Brock, Sabapathy Balasubramanian and Malcolm W.R. Reed. We thank the SEARCH and EPIC teams. SKKDKFZS: SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS: Ewa Putresza. UCIBCS: Irene Masunaka. UKBGS: Breast Cancer Now and the Institute of Cancer Research and NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. WHI: investigators and staff for their dedication. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community ' s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 -the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. ABCFS was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009-4363; 2015-7632]. The ABCTB was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The work of the BBCC was partly funded by ELANFond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). For the BCFRNY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. For BIGGS, ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. The BREOGAN is funded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI17/00918/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI12/00070). The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPICOxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPICOxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. Prof D Gareth Evans is supported by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). The GC-HBOC is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases, project numbers 713241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 1729-06014 and 17-44-020498. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. LMBC is supported by the "Stichting tegen Kanker." The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5x1000"). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous.pngt from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was supported by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. The NBCS has received funding from the K.G. Jebsen Centre for Breast Cancer Research; the Research Council of Norway grant 193387/V50 (to A-L Borresen-Dale and V.N. Kristensen) and grant 193387/H10 (to A-L Borresen-Dale and V.N. Kristensen), South Eastern Norway Health Authority (grant 39346 to A-L Borresen-Dale) and the Norwegian Cancer Society (to A-L Borresen-Dale and V.N. Kristensen). The NC-BCFR and OFBCR were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The NCBCS was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation and the special Governmental EVO funds for Oulu University Hospital-based research activities. The ORIGO study was supported by the Dutch Cancer Society (RUL 19971505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRINL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCS was supported by Sheffield Experimental Cancer Medicine Centre and Breast Cancer Now Tissue Bank. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council (SIMPLER, VR 2017-00644). The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WHI program is funded by the National Heart, Lung, and Blood Institute, the US National Institutes of Health and the US Department of Health and Human Services (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). This work was also funded by NCI U19 CA148065-01. ; Sí
A propósito de Andrés López Bermúdez, Jorge Zamalea. Enlace de mundos. Quehacer literario y cosmopolitismo (1905-1969), Bogotá, Universidad del Rosario, 2014, 584 pp. La tesis doctoral de Andrés López Bermúdez que se publica bajo este título, constituye una contribución (casi) conclusiva, de mérito excepcional, en los estudios de la historia intelectual colombiana. La biografía intelectual sobre el escritor bogotano Jorge Zalamea Borda, nacido en el marco de la Plaza de una Bogotá al principio del siglo XX, como atada a las más rancias tradiciones señoriales, y muerto sesenta y cinco años después, en medio de una sociedad que había experimentado los más profundos cambios pensables en este lapso, es una radiografía apasionante del hombre, del oficio del escritor, de la sociedad que lo hace posible y trata de negarlo, de la situación límite, en los más diversos escenarios públicos en los que actúa y desea vehementemente influir con sus escritos, con su fuerte personalidad moral y sus armas asociativas. La tesis doctoral de Andrés López hace parte ya de las biografías intelectuales más destacadas, como Andrés Bello: la pasión por el orden de Iván Jaksic, Vida de Sarmiento de Allison Williams Bunkley, Un escritor entre la gloria y las borrascas: vida de Juan Montalvo de Galo René Pérez, Horizonte humano: vida José Eustasio Rivera de Eduardo Neale-Silva, La introducción del pensamiento moderno en Colombia. El caso de Luis E. Nieto Arteta de Gonzalo Cataño, o Gabriel García Márquez, una vida de Gerald Martins —llena de exotismos. Jorge Zalamea, tal como queda retratado en la investigación de López Bermúdez en sus múltiples facetas, es el hombre del cambio, el escritor que afronta la vertiginosa transformación de una sociedad —de la sociedad señorial a la sociedad de masas—, que sueña dirigir a la luz de sus ideales liberales y que se empeña en enfrentar con todos sus vicios, traumas y rémoras. El problema de este empeño biográfico, primer escalón de una historia intelectual, no es tanto motivar al lector a seguir un periplo vital cumplido y ejemplar —la llamada "ilusión biográfica"—, sino el de ver los quiebres y discontinuidades de la vida "heroica" de un escritor en medio del abrupto cambio que se opera en los moldes convencionales de la época en que nació, dominados por la reacción conservadora ultramontana de Miguel Antonio Caro y compañía (1885-1930). Hoy no es difícil a los colombianos imaginar esa sociedad parroquial dominada por una élite cerrada, pagada de sus privilegios reales, virtuales o sobre todo fingidos, que domina una masa de mestizos que vivían o vegetaban literalmente en la miseria, corroída por la ignorancia, la desnutrición y la sífilis (el 70% la padecían). La Atenas Suramericana era todo lo contrario que consagró el ultraconservador santanderino Marcelino Menéndez y Pelayo. Era en verdad una cloaca, mal iluminada, sin alcantarillados, insegura. Pero al margen, o por encima de esta masa social, estaba la otra sociedad minoritaria, compuesta casi toda de blancos —se estimaban hispano-descendientes—, que se cultivaban desde la infancia en la casa y colegios particulares en el dominio del latín, las literaturas clásicas y españolas del Siglo del Oro, que observaban las normas éticas del catolicismo estrictamente, y seguían los consejos de Rafael María Carrasquilla en Ensayo sobre la doctrina liberal —versión nacional del furibundo libro de Félix Sardá y Salvany El liberalismo es pecado. En esta cima social, como señorito bogotano, nació Zalamea, pero no ha de morir adscrito a su origen social y a la orientación dominante de su clase —como suele mayoritariamente suceder. Jorge Zalamea llega al mundo el año en que el general Rafael Reyes sube a la presidencia. La pesadilla de la Guerra de los Mil Días y la pérdida de Panamá requerían una reconducción de la nación. Esa presidencia quiso conciliar los términos de los feroces odios bipartidistas y tomar conciencia de que, ante el poderío norteamericano, había que jugar con las cartas de unas reformas decisivas, por encima de los partidos. La nación colombiana a principios del siglo XX estaba literalmente destrozada y amenazada seriamente de seguirse fragmentado. Quizá el signo de este cambio lo refleja, en el plano intelectual o campo que más nos incumbe, la aparición de la Revista Contemporánea, dirigida por Baldomero Sanín Cano, o el libro del general Rafael Uribe Uribe Por la América del Sur. Jorge Zalamea, nos lo recrea Andrés López, nace en un caserón de la Plaza de Bolívar, de cuatro pisos, "pretenciosamente moderno". Él mismo poeta nos recuerda su balcón, luego cómo desde allí veía un árbol que se semejaba un velero. Niño privilegiado, desde muy temprano Zalamea se asomó al universo de la lectura. La fantasía infantil fue estimulada por las aventuras de Emilio Salgari y la saga de Pinocho. La figura de Chaplin también suscitó su asombro. En el colegio fundó un periódico. La primera incursión pública de Zalamea a la vida literaria fue como integrante de Los Nuevos. El grupo literario —en que participaron los Lleras Camargo, León de Greiff, Luis Tejada, Luis Vidales, Rafael Maya o Germán Arciniegas— se pretendió nuevo frente a los Centenaristas y crearon la revista Los Nuevos (1925). Las lecturas representativas, que nos anota el investigador López Bermúdez, son Maurrás y Barrés, Gide, Valéry, Rimbaud, Mallarmé, que en todo caso no aseguraba una cohesión de ideas o un propósito definido. La heterogeneidad de la agrupación hizo posible que allí también figuraran Silvio Villegas, Jorge Eliécer Gaitán, Gabriel Turbay y Darío Echandía —muchos de los cuales vendrían de la provincia a la capital—, que serían los protagonistas de ideas, sucesos y corrientes totalmente opuestas en la vida pública en las décadas siguientes. Como dice López Bermúdez quizá solo Zalamea y De Greiff fueron los dos escritores que supieron mantener más firme, en las décadas posteriores, la jerarquía y los anhelos renovadores estéticos de la agrupación literaria Los Nuevos. De mayor interés es, para el lector hoy, el primer periplo de Zalamea como artista vagabundo por Centroamérica, México y España. La ruptura juvenil con la parroquial Colombia, lo lleva a Costa Rica y Guatemala. Ese primer viaje, pues, esa asignatura del intelectual —que desde el Wilhelm Meister de Goethe— le resulta constitutiva en su formación: es el viaje a tierras lejanas, donde conoce otras gentes, otros intelectuales y otras mujeres, es decir, los insumos fundamentales de una cultura más ampliada. El joven apasionado Jorge Zalamea inicia así tempranamente el viaje que le fue posible a Baldomero Sanín Cano solo viejo, a José Eustasio Rivera solo para morir en Nueva York, a J. A. Osorio Lizarazo para servir a Perón y Trujillo, o se le negó a Tomás Carrasquilla por quiebra o a Miguel A. Caro —tal vez por empecinamiento anacrónico. El viaje de Jorge Zalamea es tratado aquí no como episodio turístico, sino precisamente como lo que es: una institución intelectual. Es el viaje que nos libera de los prejuicios o que debe contribuir a ello. Para la época —y quizá hasta hoy— era una institución para los privilegiados que generalmente lo usaba, según lo recuerda Ángel Rama, para echarse definitivamente a perder. El viaje es en Zalamea lo que fue para Bello, Bolívar, Sarmiento, Montalvo, Rubén Darío, Martí, Joaquim Nabuco, González Prada, Picón Salas o Alfonso Reyes, es decir, la ocasión de aprender, abrir horizontes intelectuales, ponerse al tanto de experiencias inéditas e inusitadas, en todo caso, imposibles de vivir en nuestro estrecho medio. El viaje es en Zalamea, como es aquí tan profusa y seriamente documentado, la prueba de fuego para definir una vocación prematura y sentar las bases de una actividad literaria de gran significación para Colombia. Zalamea entabla en ese primer periplo viajero fuertes amistades en México con Xavier Villaurrutia, Jaime Torres Bodet, Carlos Pellicer o Gilberto Owen —particularmente con este. Tras retornar a Colombia de este viaje desde agosto de 1925 a abril de 1927, se decide a publicar su primera obra El regreso de Eva, que "le tomó ocho años de trabajo". No gozó, con todo, esta pieza dramatúrgica de aceptación. Zalamea, como contrapartida, se consagra a la crítica literaria, con un ánimo profesional casi inédito en nuestro medio —a excepción de Sanín Cano o Carlos A. Torres. Viaja a España —quizá agotado del medio provinciano— a finales de ese mismo año. Allí va a cimentar su personalidad intelectual y su obra literaria. La estrecha amistad con el poeta, universalmente reconocido, Federico García Lorca, es parte del inventario de esos años en la Península. Lo es también su labor como traductor del inglés, francés e italiano, seguida con interés puntual. Zalamea traduce a Joseph Conrad o D'Annunzio. Se esconden sus traducciones bajo el nombre de Ricardo Baeza, quien gozaba de gran prestancia en la escena literaria peninsular y gracias a ello puede cobrar más. Pero fue sin duda la amistad con García Lorca, quien le dedica su "Poema de la soleá, tierra seca", una fecunda ocasión en el curso de la consolidación de la personalidad literaria de Jorge Zalamea en tierras españolas. Esta amistad, anota López Bermúdez, fue "entrañable y afectuosa", el mismo poeta bogotano lo llama "el mejor de mis amigos". La correspondencia íntima entre ambos —en que se intercambia penas, pesares y proyectos líricos— y los testimonios de contemporáneos certifican la especial relación que los unía. También esta amistad mantuvo y amplió el amor de Zalamea por el teatro. En la estancia de España, que se prolonga hasta 1932 fecha en que es nombrado diplomático en Londres hasta 1934, Jorge Zalamea contrae nupcias con la bella, inteligente y a la postre trágica Amelia Costa. Este cargo diplomático, cuyas funciones parecen difusas —¿qué hace en realidad un agregado cultural?—, le permite intercambiar favores, por ejemplo con Germán Arciniegas, de cuyo libro El estudiante de la mesa redonda, recibe cincuenta ejemplares que distribuye entre sus amistades españolas, como Unamuno, García Lorca, Ortega y Gasset, Recasens Siches, etc. También hace leer a su amigo García Lorca La marquesa de Yolombó de Carrasquilla, quien a decir del mismo Zalamea, "quedó deslumbrado". Arciniegas a su vez distribuyó en Bogotá, como compensación, el folleto De Jorge Zalamea a la juventud colombiana. Este segundo periplo viajero, concluye en 1934. Zalamea había ya absorbido la sustancia cultural de Europa que lo habilitaba como un gran conocedor de espacios literarios, de ideas, corrientes en América Latina y Europa. Tenía 29 años y se alistó en las filas de la alta burocracia del gobierno de López Pumarejo —el único en el siglo XX que ensayó y puso en práctica políticas modernizadoras a una elite sustancialmente retrograda, de inmensas injusticias y fuertemente aferrada a los dogmas católicos— y colmó así uno de sus sueños de hombre de letras. Los servicios, como intelectual comprometido, en el gobierno de la "Revolución en marcha", como se conoce este periodo, cuyo impulso se concentró entre abril y diciembre de 1936, se resumen en su participación en la Comisión de Cultura Aldeana, de la que surgió su monografía El Departamento de Nariño: esquema para una interpretación sociológica; y en sus cargos en la Secretaría del Ministerio de Educación y de la Presidencia de la República. La relación con el curtido líder liberal López Pumarejo —había nacido en Honda en 1886— fue definitiva para asumir el rol distintivo en el marco público nacional: Jorge Zalamea como un combatiente de las ideas liberales de renovación social. La puntual realización que lo distinguió y que fue para Zalamea permanente motivo de satisfacción: la colaboración en la creación de la Universidad Nacional de Colombia, hito decisivo en la vida universitaria y académica del país —la vieja Universidad Nacional de 1867 de Manuel Ancízar había prácticamente dejado de existir bajo la Regeneración. Entorno a la construcción de la Ciudadela Universitaria o Ciudad Blanca, creada en 1936 con el diseño del arquitecto y urbanista alemán de la Escuela de Bauhaus, Leopoldo Rother, se formó una batalla campal de ideas. Mientras la Iglesia y El Tiempo se opuso —lo que no obsta que Eduardo Santos haya ayudado al jesuita Félix Restrepo a conseguir la sede de la Universidad Javeriana, pilar anti-liberal o anti-lopista— a la creación de la Universidad Nacional y argumentan ateísmo o despilfarro, Zalamea mantuvo firme su defensa de la educación pública superior. Al tiempo que cumplía sus funciones públicas, Zalamea no desaprovechó para promocionar su obra, difundirla en América Latina en Perú con Luis Alberto Sánchez, en Chile con Pablo Neruda, en Argentina con Victoria Ocampo. Fue esta deslumbrante actuación pública, en un escenario encendido de pasiones políticas, trampolín para su figuración literaria y ocasión para su fama literaria. La década de los cuarenta es para Zalamea más bien época de tertulias y debates literarios. En ellos se destaca su defensa de la agrupación poética Piedra y Cielo, en cuya cabeza se pone Eduardo Carranza. Publica su "ensayo filantrópico" como lo califica Andrés López El hombre, náufrago del siglo XX, y sobre todo son sus intensos y no menos duros —afectivamente: se suicida su mujer— años como embajador en México, a partir de 1943 durante el segundo periodo presidencial de López Pumarejo. Entra Zalamea allí en contacto con el connotado ensayista Alfonso Reyes, para quien gestiona la Cruz de Boyacá, y con Daniel Cossio Villegas, el director del Fondo de Cultura Económica, con quien diseña un listado de posibles obras colombianas que no van a ser, a la postre, publicadas —la no publicación de autores colombianos en el Fondo confirma el aislamiento cultural del país en esas décadas decisivas de modernización urbana y rezago político atávico. Publica la edición mexicana de La vida maravillosa de los libros. También son años de cocteles y excesos de bohemia, de angustia existencial. El papel que cumplió Jorge Zalamea, años después, tras su retorno de Embajador en México, luego del asesinato de Gaitán y la amenaza del ascenso del obseso franquista Laureano Gómez al poder, que tenía los visos de una hecatombe del proyecto liberal, cobra el aspecto de una lucha abierta, de vida o muerte. Zalamea fue en los años oscuros de las dictaduras de Mariano Ospina Pérez —cierra el congreso en 1949 y militariza buena parte de las poblaciones colombianas que da origen a un cadena de violencia que aún no ha concluido— la voz de la disidencia. Fue perseguido, estigmatizado, encarcelado. Tuvo que dar el paso de huir del clima asfixiante del país, dominando por la mal llamada Violencia: era esta una maquinaria de terrorismo de Estado, impulsada y profundizada directa y abiertamente por Laureano Gómez para borrar de la fase de la tierra colombiana el liberalismo y restaurar una Cristilandia a sangre y fuego. En Buenos Aires como exiliado, se topa Jorge Zalamea, en realidad, por intermediación del poeta de filiación comunista Luis Vidales, con el altísimo cargo diplomático-cultural de Secretario del Consejo Mundial por la Paz (CMP). El CMP, instituido en 1949 tras la Segunda Guerra Mundial, era una organización pro-soviética destinada a promover las alianzas entre los pueblos, fomentar la paz mundial y servir de plataforma para el intercambio de artistas e intelectuales de todo el mundo, doctrinaria o afínmente afectos al régimen de Moscú. El cargo llegó como caído del cielo y casi por azar. Zalamea no era un comunista —difícilmente se le puede calificar socialista en alguna de sus variantes— pero creía en la dignidad del hombre, en la necesidad de establecer políticas sociales modernizadoras y se autodenominaba anti-belicista; del otro lado, estaba el Congreso por la Libertad de la Cultura, auspiciado por el Departamento de Estado norteamericano y la CIA, en cuyas filas militaba el liberal santista Germán Arciniegas. Para la época en que Zalamea era Secretario de CMP, lo era para CLC el compositor ruso Nikolas Nabokov, quien era apoyado por Robie Macauley, agente de la CIA y editor de Playboy. Zalamea llega a este cargo por razones difíciles de hilar en una argumentación sólida. Su personalidad literaria se acompasaba por su personalidad política y sobre todo por su moral. Su modelo intelectual era una mezcla de la herencia del poeta modernista, del bohemio y genio poético de Rubén Darío, arrojado al azar de las circunstancias políticas, y el protagonista de un cambio social por medio del estudio social, la propaganda política sólida y el uso de los medios de divulgación más afines a los propósitos de un cambio social más justo y equilibrado. Por razón de espacio, no podría seguir estas nuevas y muy resonantes actividades de Jorge Zalamea, en la que destacó solo su iniciativa de galardonar con el Premio Lenin de la Paz a su compatriota que más lo merecía, sin duda, Baldomero Sanín Cano. También el mismo Jorge Zalamea, con apoyo de Miguel Ángel Asturias y Pablo Neruda, contribuye a que el poeta bogotano, por lo demás muy corto de recursos económicos y minado por dolencias hepáticas, obtenga ese codiciado premio incluido el alto monto de 28.000 dólares para 1968. Zalamea fue, pues, poeta, traductor, ensayista, crítico literario, dramaturgo, polemista, sociólogo, editor, periodista, mediador y promotor cultural, diplomático, ministro, conferencista, profesor universitario. También fue bohemio, corresponsal asiduo, activísimo secretario del Consejo Mundial de la Paz, acerbo crítico, intransigente enemigo y militante convencido, como lo insistió no pocas veces, de la causa antibélica. Estas múltiples actividades, y estos simultáneos roles intelectuales y sociales, resultaron no siempre coherentes o consecuentes. Es difícil sino imposible cumplir a satisfacción en tantos frentes, sobre todo cuando los escenarios públicos dominantes son diversos, están en tensiones continuas y sus orientaciones ideológicas cambian súbitamente. La vida de Jorge Zalamea está tirada por un hilo o hecha de un nudo grueso de dificultades, sobresaltos, ansiedades, crisis, inestabilidades psicológicas. Nunca parece, conforme este formidable retrato de Andrés López Bermúdez, que está lejos de un cuadro psiquiátrico, pero que inevitable da material para ello, estar Zalamea satisfecho con su obra literaria. No está libre de presiones económicas; más bien se encuentra atado a una inseguridad de diversos orígenes, a una cierta ingobernabilidad de los resortes de la existencia que lo lleva a la recurrencia a la vida bohemia, al alcoholismo, al desfogue por amores "ilícitos". Hay como una tragedia labrada, un sino de incontenibles tintas negras. Pero hay otro componente en Zalamea. Hay también un impulso ético a toda prueba, un afán inclaudicable de perfeccionamiento artístico, un activismo fáustico por una patria mejor, por un mejoramiento de las relaciones sociales, de las condiciones de existencia de una sociabilidad dominada por el disimulo, la hipocresía, la perversidad. Zalamea luchó contra el fanatismo, sin verse del todo libre de los prejuicios culturales que lo hacía posible y lo estimulaba. Fue machista, fue pagado de sus privilegios —más de su inteligencia que de sus orígenes sociales—, resultó a veces vacilante y repelente, cuando quizá se precisaba más tacto y tino para decidir sobre situaciones inconmensurables. Hubo un signo de inestabilidad, de "mercurialismo" en todo su ser artístico e intelectual. Zalema no fue un hombre de partido, ni liberal ni comunista; o mejor, antepuso siempre su personalidad de artista —un modelo como heredado de la España canovista: pienso en Emilio Castelar o Juan Valera, o quizá del modelo que él mismo experimentó en España con los volubles Unamuno y Azorín a la cabeza— que presupone la superioridad de la inteligencia por encima de todo otro imponderable cultural. Zalamea fue un secreto saint-simoniano, que encontraba en la exaltación pública de la inteligencia, el deseo de figurar en su Parlamento Newton. Este es el punto quizá más problemático de una personalidad sellada, como la de Jorge Zalamea, por una tradición medio-legible. Mitad obra de la tradición del poeta como esteta de la sociedad y otra mitad reformador social gracias a su labor de hombre estético. En este sentido quizá Sanín Cano, quien nació medio siglo antes, tuvo un sentido de las proporciones más ajustado. Los dos, sin embargo, apenas pudieron reconocer el papel protagónico, no de los movimientos sociales de izquierda radical, sino el papel de la inteligencia radical de izquierda justo en la redefinición del intelectual como figura marginal. Sólo con despecho aceptó, un Ezequiel Martínez Estrada —diez años mayor que Zalamea—, esta situación cuando se decidió a vivir a Cuba en 1961. Pocos años después comprendió que la maquinaria de la revolución cubana devoraba también a sus intelectuales comprometidos; que no había un sitio específico para los intelectuales en la marejada revolucionaria, como no lo había para ese grupo en el mundo burgués desde Baudelaire. Algo más "románticamente" que Martínez Estrada, Jorge Zalamea siguió insistiendo, pero desde Bogotá, en colaborar para la causa de Fidel Castro. Pero este gesto de compromiso no pasaba de una elegante manera de aceptar que las cosas habían cambiado muy profundamente. Su rechazo a la conquista del poder por las armas fue síntoma de ello o parte de su inteligencia crítica. Zalamea pidió a la juventud universitaria conquistar el poder por la inteligencia en un país más bien de mulas resabiadas. Su defensa a la revolución cubana o su crítica al México ensangrentado de la masacre de Tlatelolco, eran gestos desde la distancia. En casa sabemos que Jorge Zalamea se peleó agria y justificadamente con el pontífice del Nadaísmo Gonzalo Arango —quizá percibiendo que ese movimiento era un tardío reflejo provinciano de "pour épater le bourgeois", en el marco de la intensa masificación urbana en un estadio cultural nutrido del catolicismo barroco—, mientras no lo encontramos figurado en esas laberínticas discusiones del marxismo-leninismo que produjo el MOEC, FUAR, ELN, Grupos M-L, MOIR, COR y otro medio centenar de pequeñas organizaciones campesinas, obreras, guerrilleas y estudiantiles, desde mediados de los años sesenta. Ya parecía ser un intelectual de otra generación y su voz, que sonaba en los discos de acetato por millares —hay algo anacrónico en La voz de Jorge Zalamea presenta la poesía ignorada—, poco a poco dejó de tener la pertinencia política que él deseó para su obra literaria. La investigación doctoral Jorge Zalamea, enlace de mundos. Quehacer literario y cosmopolitismo (1905-1969) fue posible gracias a la circunstancia de que el hijo del poeta bogotano, Alberto Zalamea Costa, pudo obtener en 2007, luego de ser abandonado en un sótano por 38 años, el archivo de su polémico padre. Los numerosos documentos que son tratados en esta investigación, conforme lo confiesa el profesor López Bermúdez, son apenas una parte de la montaña de cartas, papeles y documentos de muy diversa naturaleza historiográfica, encontrados allí. La paciencia para ordenarlos, clasificarlos, analizarlos, y al fin, darles un orden argumentativo fascinante, se contrae a estas casi 600 densas páginas. Sólo quiero reiterar el honor que se me concede al presentarlas ante ustedes. Es una desproporción conceptual insinuar que Jorge Zalamea Borda estaba esperando a Andrés López Bermúdez para hacerse comprensible. Sin embargo, por pasajes lo sentimos dramáticamente así. Juan Guillermo Gómez García(Universidad de Antioquía/Universidad Nacional)
Only Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715680/ ; Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95% CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants. ; We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. We acknowledge all contributors to the COGS and OncoArray study design, chip design, genotyping, and genotype analyses. ABCFS thank Maggie Angelakos, Judi Maskiell, Gillian Dite. ABCS thanks the Blood bank Sanquin, The Netherlands. ABCTB Investigators: C.L.C., Rosemary Balleine, Robert Baxter, Stephen Braye, Jane Carpenter, Jane Dahlstrom, John Forbes, Soon Lee, Deborah Marsh, Adrienne Morey, Nirmala Pathmanathan, Rodney Scott, Allan Spigelman, Nicholas Wilcken, Desmond Yip. Samples are made available to researchers on a non-exclusive basis. The ACP study wishes to thank the participants in the Thai Breast Cancer study. Special Thanks also go to the Thai Ministry of Public Health (MOPH), doctors and nurses who helped with the data collection process. Finally, the study would like to thank Dr Prat Boonyawongviroj, the former Permanent Secretary of MOPH and Dr Pornthep Siriwanarungsan, the Department Director-General of Disease Control who have supported the study throughout. BBCS thanks Eileen Williams, Elaine Ryder-Mills, Kara Sargus. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Jose Esteban Castelao, Angel Carracedo, Victor Munoz Garzon, Alejandro Novo Dominguez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Pena Fernandez, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), Jose Antunez, Maximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigacion Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquin Gonzalez-Carrero and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. The CAMA study would like to recognize CONACyT for the financial support provided for this work and all physicians responsible for the project in the different participating hospitals: Dr. German Castelazo (IMSS, Ciudad de Mexico, DF), Dr. Sinhue Barroso Bravo (IMSS, Ciudad de Mexico, DF), Dr. Fernando Mainero Ratchelous (IMSS, Ciudad de Mexico, DF), Dr. Joaquin Zarco Mendez (ISSSTE, Ciudad de Mexico, DF), Dr. Edelmiro Perez Rodriguez (Hospital Universitario, Monterrey, Nuevo Leon), Dr. Jesus Pablo Esparza Cano (IMSS, Monterrey, Nuevo Leon), Dr. Heriberto Fabela (IMSS, Monterrey, Nuevo Leon), Dr. Fausto Hernandez Morales (ISSSTE, Veracruz, Veracruz), Dr. Pedro Coronel Brizio (CECAN SS, Xalapa, Veracruz) and Dr. Vicente A. Saldana Quiroz (IMSS, Veracruz, Veracruz). CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgard Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. COLBCCC thanks all patients, the physicians Justo G. Olaya, Mauricio Tawil, Lilian Torregrosa, Elias Quintero, Sebastian Quintero, Claudia Ramirez, Jose J. Caicedo, and Jose F. Robledo, the researchers Ignacio Briceno, Fabian Gil, Angela Umana, Angela Beltran and Viviana Ariza, and the technician Michael Gilbert for their contributions and commitment to this study. Investigators from the CPSII cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. CTS Investigators include Leslie Bernstein, S.L.N., James Lacey, Sophia Wang, and Huiyan Ma at the Beckman Research Institute of City of Hope, Jessica Clague DeHart at the School of Community and Global Health Claremont Graduate University, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Peggy Reynolds, at the Department of Epidemiology and Biostatistics, University of California San Francisco, H.A-C, A.Z., and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Krober and LIFE -Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tubingen, Germany [H.B., W-Y.L.], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [H. B.], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy - EXC 2180 -390900677, Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [UH], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bruning, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer and Johann H. Karstens. HEBCS thanks Sofia Khan, Johanna Kiiski, Kristiina Aittomaki, Rainer Fagerholm, Kirsimari Aaltonen, Karl von Smitten, Irja Erkkila. HKBCS thanks Hong Kong Sanatorium and Hospital, Dr Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation, National Institute of Health 1R03CA130065 and the North California Cancer Center for support. HMBCS thanks Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myohanen, Helena Kemilainen. We thank all investigators of the KOHBRA (Korean Hereditary Breast Cancer) Study. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB "Georgi D. Efremov), Emilija Lazarova (University Clinic of Radiotherapy and Oncology), Katerina Kubelka-Sabit, Mitko Karadjozov (Adzibadem-Sistina Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group): Bernard Peissel, Jacopo Azzollini, Dario Zimbalatti, Daniela Zaffaroni, Bernardo Bonanni, Mariarosaria Calvello, Davide Bondavalli, Aliana Guerrieri Gonzaga, Monica Marabelli, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines, Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de QuebecUniversite Laval Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J. S. is Chair holder of the Canada Research Chair in Oncogenetics. MYBRCA thanks study participants and research staff (particularly Patsy Ng, Nurhidayu Hassan, Yoon Sook-Yee, Daphne Lee, Lee Sheau Yee, Phuah Sze Yee and Norhashimah Hassan) for their contributions and commitment to this study. The NBCS Collaborators would like to thank the Oslo Breast Cancer Research Consortium, OSBREAC (breastcancerresearch. no/osbreac/), for providing samples and phenotype data. NBHS and SBCGS thank study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses' Health Study and Nurses' Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander, Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. The ORIGO survival data were retrieved from the Leiden hospital-based cancer registry system (ONCDOC) with the help of Dr. J. Molenaar. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner. The ethical approval for the POSH study is MREC/00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SGBCC thanks the participants and research coordinator Ms Tan Siew Li. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community's Seventh Framework Programme under grant agreement number 223175 (Grant Number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec and the PSR-SIIRI-701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement No. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 -the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. The Australian Breast Cancer Family Study (ABCFS), BCFR-NY, BCFR-PA, BCFR-UTAH, the Northern California Breast Cancer Family Registry (NCBCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. C.L.C is a NHMRC Principal Research Fellow. The ACP study is funded by the Breast Cancer Research Trust, UK and KM and AL are supported by the NIHR Manchester Biomedical Research Centre and by the ICEP ("This work was also supported by CRUK [grant number C18281/A19169]"). The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia and acknowledges funding from the National Breast Cancer Foundation (J.S.). The BREast Oncology GAlician Network (BREOGAN) is funded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I+ D e I + D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CAMA study was funded by Consejo Nacional de Ciencia y Tecnologia (CONACyT) (SALUD-2002-C01-7462). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant #313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. COLBCCC is supported by the German Cancer Research Center (DKFZ), Heidelberg, Germany. Diana Torres was in part supported by a postdoctoral fellowship from the Alexander von Humboldt Foundation. The American Cancer Society funds the creation, maintenance, and updating of the CPSII cohort. The CTS was supported by the California Breast Cancer Act of 1993, the California Breast Cancer Research Fund (contract 97-10500) and the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. HAC receives support from the Lon V Smith Foundation (LVS39420). The University of Westminster curates the DietCompLyf database funded by the charity Against Breast Cancer (Registered Charity No. 1121258) and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. DGE is supported by the all Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: R.K.S., Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e.V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, by the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HERPACC was supported by MEXT Kakenhi (No. 170150181 and 26253041) from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan, by National Cancer Center Research and Development Fund, and "Practical Research for Innovative Cancer Control (15ck0106177h0001)" from Japan Agency for Medical Research and development, AMED, and Cancer Bio Bank Aichi. The HMBCS and HUBCS were funded by the German Research Foundation (Do761/10-1) and by the Rudolf Bartling Foundation. The HUBCS was further supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. The KOHBRA study was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 1020350; 1420190). LMBC is supported by the 'Stichting tegen Kanker'. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov" and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e. V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was supported by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the " CIHR Team in Familial Risks of Breast Cancer" program -grant #CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade - grant #PSR-SIIRI-701. MYBRCA is funded by research grants from the Malaysian Ministry of Higher Education (UM. C/HlR/MOHE/06) and Cancer Research Malaysia. MYMAMMO is supported by research grants from Yayasan Sime Darby LPGA Tournament and Malaysian Ministry of Higher Education (RP046B-15HTM). The NBCS has received funding from the K.G. Jebsen Centre for Breast Cancer Research; the Research Council of Norway grant 193387/V50 (to A-L Borresen-Dale and V.N.K.) and grant 193387/H10 (to A-L Borresen-Dale and V. N. K.), South Eastern Norway Health Authority (grant 39346 to A-L Borresen-Dale) and the Norwegian Cancer Society (to A-L Borresen-Dale and V. N. K.). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Carolina Breast Cancer Study (NCBCS) was funded by Komen Foundation, the National Cancer Institute (National Cancer Institute CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NGOBCS was supported by the National Cancer Center Research and Development Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, UMCA182910, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scientific development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network U19 CA148065. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347). SGBCC is funded by the NUS start-up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort StudiesMulti-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/1/21/19/425. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ohio State University Comprehensive Cancer Center. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WAABCS study was supported by grants from the National Cancer Institute of the National Institutes of Health (R01 CA89085 and P50 CA125183 and the D43 TW009112 grant), Susan G. Komen (SAC110026), the Dr. Ralph and Marian Falk Medical Research Trust, and the Avon Foundation for Women.
Abstract Aim: This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic. Methods: This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centres entered data from their first recorded case of COVID-19 until 19 April 2020. The primary outcome was 30-day mortality. Secondary outcomes included anastomotic leak, postoperative SARS-CoV-2 and a comparison with prepandemic European Society of Coloproctology cohort data. Results: From 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty-day mortality was 1.8% (38/2073), the incidence of postoperative SARS-CoV-2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS-CoV-2 (14/1601, 0.9%) and highest in patients with both a leak and SARS-CoV-2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58–14.06), postoperative SARS-CoV-2 (16.90, 7.86–36.38), male sex (2.46, 1.01–5.93), age >70 years (2.87, 1.32–6.20) and advanced cancer stage (3.43, 1.16–10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%). Conclusion: Surgeons need to further mitigate against both SARS-CoV-2 and anastomotic leak when offering surgery during current and future COVID-19 waves based on patient, operative and organizational risks. ; Appendix 1 Writing group (*denotes joint first authors) Elizabeth Li*, James C. Glasbey*, Dmitri Nepogodiev*, Joana F. F. Simoes*, Omar M. Omar, Mary L. Venn, Jonathan P. Evans, Kaori Futaba, Charles H. Knowles, Ana Minaya-Bravo, Helen Mohan, Manish Chand, Peter Pockney, Salomone Di Saverio, Neil Smart, Abigail Vallance, Dale Vimalachandran, Richard J. W. Wilkin, Aneel Bhangu (Overall guarantor). 2 Statistical analysis Omar M. Omar (Lead statistician), Elizabeth Li, James C. Glasbey, Aneel Bhangu. 3 CovidSurg Operations Committee Kwabena Siaw-Acheampong, Ruth A. Benson, Edward Bywater, Daoud Chaudhry, Brett E. Dawson, Jonathan P. Evans, James C. Glasbey, Rohan R. Gujjuri, Emily Heritage, Conor S. Jones, Sivesh K. Kamarajah, Chetan Khatri, Rachel A. Khaw, James M. Keatley, Andrew Knight, Samuel Lawday, Elizabeth Li, Harvinder S. Mann, Ella J. Marson, Kenneth A. McLean, Siobhan C. Mckay, Emily C. Mills, Dmitri Nepogodiev, Gianluca Pellino, Maria Picciochi, Elliott H. Taylor, Abhinav Tiwari, Joana F. F. Simoes, Isobel M. Trout, Mary L. Venn, Richard J. W. Wilkin, Aneel Bhangu. 4 International Cancer Leads (*denotes specialty principal Investigator) James C. Glasbey (Chair); Colorectal: Neil J. Smart*, Ana Minaya-Bravo*, Jonathan P. Evans, Gaetano Gallo, Susan Moug, Francesco Pata, Peter Pockney, Salomone Di Saverio, Abigail Vallance, Dale Vimalchandran. 5 Dissemination Committee Joana F. F. Simoes (Chair); Tom E. F. Abbott, Sadi Abukhalaf, Michel Adamina, Adesoji O. Ademuyiwa, Arnav Agarwal, Murat Akkulak, Ehab Alameer, Derek Alderson, Felix Alakaloko, Markus Albertsmeiers, Osaid Alser, Muhammad Alshaar, Sattar Alshryda, Alexis P. Arnaud, Knut Magne Augestad, Faris Ayasra, José Azevedo, Brittany K. Bankhead-Kendall, Emma Barlow, David Beard, Ruth A. Benson, Ruth Blanco-Colino, Amanpreet Brar, Ana Minaya-Bravo, Kerry A. Breen, Chris Bretherton, Igor Lima Buarque, Joshua Burke, Edward J. Caruana, Mohammad Chaar, Sohini Chakrabortee, Peter Christensen, Daniel Cox, Moises Cukier, Miguel F. Cunha, Giana H. Davidson, Anant Desai, Salomone Di Saverio, Thomas M. Drake, John G. Edwards, Muhammed Elhadi, Sameh Emile, Shebani Farik, Marco Fiore, J. Edward Fitzgerald, Samuel Ford, Tatiana Garmanova, Gaetano Gallo, Dhruv Ghosh, Gustavo Mendonça Ataíde Gomes, Gustavo Grecinos, Ewen A. Griffiths, Madalegna Gründl, Constantine Halkias, Ewen M. Harrison, Intisar Hisham, Peter J. Hutchinson, Shelley Hwang, Arda Isik, Michael D. Jenkinson, Pascal Jonker, Haytham M. A. Kaafarani, Debby Keller, Angelos Kolias, Schelto Kruijff, Ismail Lawani, Hans Lederhuber, Sezai Leventoglu, Andrey Litvin, Andrew Loehrer, Markus W. Löffler, Maria Aguilera Lorena, Maria Marta Madolo, Piotr Major, Janet Martin, Hassan N. Mashbari, Dennis Mazingi, Symeon Metallidis, Ana Minaya-Bravo, Helen M. Mohan, Rachel Moore, David Moszkowicz, Susan Moug, Joshua S. Ng-Kamstra, Mayaba Maimbo, Ionut Negoi, Milagros Niquen, Faustin Ntirenganya, Maricarmen Olivos, Kacimi Oussama, Oumaima Outani, Marie Dione Parreno-Sacdalanm, Francesco Pata, Carlos Jose Perez Rivera, Thomas D. Pinkney, Willemijn van der Plas, Peter Pockney, Ahmad Qureshi, Dejan Radenkovic, Antonio Ramos-De la Medina, Keith Roberts, April C. Roslani, Martin Rutegård, Irène Santos, Sohei Satoi, Raza Sayyed, Andrew Schache, Andreas A Schnitzbauer, Justina O. Seyi-Olajide, Neil Sharma, Richard Shaw, Sebastian Shu, Kjetil Soreide, Antonino Spinelli, Grant D Stewart, Malin Sund, Sudha Sundar, Stephen Tabiri, Philip Townend, Georgios Tsoulfas, Gabrielle H. van Ramshorst, Raghavan Vidya, Dale Vimalachandran, Oliver J. Warren, Duane Wedderburn, Naomi Wright, EuroSurg, European Society of Coloproctology (ESCP), Global Initiative for Children's Surgery (GICS), GlobalSurg, GlobalPaedSurg, ItSURG, PTSurg, SpainSurg, Italian Society of Colorectal Surgery (SICCR), Association of Surgeons in Training (ASiT), Irish Surgical Research Collaborative (ISRC), Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), Italian Society of Surgical Oncology (SICO). 6 Collaboratoring authors (*denotes site principal investigators) Argentina: Alurralde C., Caram E. L., Eskinazi D* (Sanatorio 9 De Julio Sa); Badra R., García J.S., Lucchini S.M.* (Sanatorio Allende). Australia: Cecire J., Salindera S.*, Sutherland A. (Coffs Harbour Health Campus); Ahn J.H., Chen S., Gauri N., Jang S., Jia F., Mulligan C., Yang W., Ye G., Zhang H. (Concord Repatriation General Hospital); Moss J.*, Richards T., Thian A., Vo U. G. (Fiona Stanley Hospital); Bagraith K., Chan E., Ho D., Jeyarajan E., Jordan S., Nolan G. J., Von Papen M., Wullschleger M. (Gold Coast University Hospital); Egoroff N., Gani J., Lott N., Pockney P.* (John Hunter Hospital); Phan D., Townend D.* (Lismore Base Hospital); Bong C., Gundara J.* (Logan Hospital); Bowman S.*, Guerra G. R. (Queen Elizabeth II Jubilee Hospital); Dudi-Venkata N. N., Kroon H. M.*, Sammour T. (Royal Adelaide Hospital); Mitchell D.*, Swinson B. (Royal Brisbane and Women's Hospital). Austria: Messner F., Öfner D.* (Medical University of Innsbruck); Emmanuel K., Grechenig M., Gruber R., Harald M., Öhlberger L., Presl J.*, Wimmer A. (Paracelsus Medical University Salzburg). Barbados: Barker D., Boyce R., Doyle A., Eastmond A., Gill R., O'Shea M., Padmore G.*, Paquette N., Phillips E., St John S., Walkes K. (Queen Elizabeth Hospital). Belgium: Flamey N., Pattyn P.* (Az Delta); Oosterlinck W.*, Van den Eynde J., Van den Eynde R. (Uz Leuven). Bulgaria: Sokolov M.* (University Hospital Alexandrovska). Canada: Boutros M.*, Caminsky N. G., Ghitulescu G. (Jewish General Hospital); Boutros M.*, Demyttenaere S.*, Garfinkle R. (St Mary's Hospital); Nessim C.*, Stevenson J. (The Ottawa Hospital). Croatia: Bačić G., Karlović D., Kršul D., Zelić M.* (University Hospital Center Rijeka); Bakmaz B., Ćoza I., Dijan E., Katusic Z., Mihanovic J.*, Rakvin I. (Zadar General Hospital). Cyprus: Frantzeskou K., Gouvas N.*, Kokkinos G., Papatheodorou P., Pozotou I., Stavrinidou O., Yiallourou A.* (Nicosia General Hospital). Czechia: Martinek L., Skrovina M.*, Szubota I. (Hospital and Oncological Centre Novy Jicin). Denmark: Ebbehøj A. L., Krarup P., Schlesinger N., Smith H.* (Bispebjerg Hospital). Egypt: Al Sayed M., Ashoush F.*, Elazzazy E., Essam E., Eweda M., Hassan E., Metwalli M., Mourad M., Qatora M. S., Sabry A.*, Samih A., Samir Abdelaal A., Shehata S.*, Shenit K. (Alexandria Main University Hospital); Attia D., Kamal N., Osman N.* (Alexandria Medical Research Institute); Alaa S., Hamza H. M., M. elghazaly S., Mohammed M. M.*, Nageh M. A., Saad M. M.*, Yousof E. A. (Assiut University Hospital); Eldaly A. S.* (El-Menshawy Hospital); Amira G., Sallam I.*, Sherief M., Sherif A. (Misr Cancer Center); Ghaly G.*, Hamdy R., Morsi A., Salem H.*, Sherif G. (National Cancer Institute); Abdeldayem H., Abdelkader Salama I.*, Balabel M., Fayed Y., Sherif A. E.* (National Liver Institute, Menoufia University). Finland: Kauppila J. H.*, Sarjanoja E. (Länsi-Pohja Central Hospital); Helminen O., Huhta H., Kauppila J. H.* (Oulu University Hospital). France: Beyrne C., Jouffret L.*, Marie-Macron L. (Centre Hospitalier Avignon); Lakkis Z.*, Manfredelli S. (CHU Besançon); Chebaro A.*, El Amrani M., Lecolle K., Piessen G.*, Pruvot F. R., Zerbib P. (CHU Lille); Ballouhey Q.*, Barrat B., Taibi A. (Chu Limoges); Bergeat D., Merdrignac A. (CHU Rennes – General Surgery); Le Roy B., Perotto L. O., Scalabre A.* (Chu Saint Etienne); Aimé A., Ezanno A.*, Malgras B. (Hia Begin); Bouche P. A.*, Tzedakis S.* (Hôpital Cochin – APHP); Cotte E., Glehen O., Kepenekian V., Passot G. (Hopital Lyon Sud); D'Urso A., Mutter D., Seeliger B.* (Strasbourg University Hospitals/IHU-Strasbourg); Bonnet S., Denet C., Fuks D., Laforest A., Pourcher G., Seguin-Givelet A.*, Tribillon E. (Institut Mutualiste Montsouris); Duchalais E.* (Nantes University Hospital). Germany: Bork U.*, Fritzmann J., Praetorius C., Weitz J., Welsch T. (Carl-Gustav-Carus University Hospital, TU Dresden); Beyer K., Kamphues C.*, Lauscher J. C., Loch F. N., Schineis C. (Charité University Medicine, Campus Benjamin Franklin); Becker R.*, Jonescheit J. (Heilig-Geist Hospital Bensheim); Pergolini I., Reim D.* (Klinikum Rechts der Isar TUM School of Medicine); Boeker C., Hakami I.*, Mall J.* (KRH Nordstadt-Siloah Hospitals); Albertsmeier M.*, Kappenberger A., Schiergens T., Werner J. (LMU Klinikum Campus Innenstadt); Nowak K.*, Reinhard T.* (Romed Klinikum Rosenheim); Kleeff J., Michalski C., Ronellenfitsch U.* (University Hospital Halle (Saale)); Bertolani E., Königsrainer A.*, Löffler M. W., Quante M.*, Steidle C., Überrück L., Yurttas C. (University Hospital Tuebingen); Izbicki J., Nitschke C., Perez D., Uzunoglu F. G.* (University Medical Center Hamburg–Eppendorf). Greece: Antonakis P., Contis I., Dellaportas D., Gklavas A., Konstadoulakis M., Memos N.*, Papaconstantinou I.*, Polydorou A., Theodosopoulos T., Vezakis A. (Aretaieion Hospital); Antonopoulou M. I., Manatakis D. K.*, Tasis N. (Athens Naval and Veterans Hospital); Arkadopoulos N., Danias N., Economopoulou P., Frountzas M., Kokoropoulos P., Larentzakis A., Michalopoulos N.*, Parasyris S., Selmani J., Sidiropoulos T., Vassiliu P. (Attikon University General Hospital); Bouchagier K.*, Klimopoulos S., Paspaliari D., Stylianidis G. (Evaggelismos General Hospital); Baxevanidou K., Bouliaris K., Chatzikomnitsa P., Efthimiou M., Giaglaras A., Kalfountzos C.*, Koukoulis G., Ntziovara A. M., Petropoulos K., Soulikia K., Tsiamalou I., Zervas K., Zourntou S. (General Hospital of Larissa 'Koutlimpaneio and Triantafylleio'); Baloyiannis I., Diamantis A., Perivoliotis K., Tzovaras G.* (General University Hospital of Larissa); Christidis P., Ioannidis O.*, Loutzidou L. (George Papanikolaou General Hospital of Thessaloniki); Karaitianos I.*, Tsirlis T. (Henry Dunant Hospital Center); Charalabopoulos A., Liakakos T., Baili E., Schizas D.*, Spartalis E., Syllaios A., Zografos C. (Laiko University Hospital); Athanasakis E., Chrysos E., Tsiaoussis I., Xenaki S.*, Xynos E.* (University Hospital of Heraklion Crete and Interclinic Hospital of Crete). Hong Kong: Futaba K.*, Ho M. F., Hon S. F., Mak T. W. C., Ng S. S. M. (Prince of Wales Hospital); Foo C. C.* (Queen Mary Hospital). Hungary: Banky B.*, Suszták N. (Szent Borbála Kórház). India: Bhat G. A., Chowdri N. A., Mehraj A.*, Parray F., Shah Z. A., Wani R. (Sher-I-Kashmir Institute of Medical Sciences); Ahmed Z., Bali R., Bhat M. A., Laharwal A., Mahmood M., Mir I., Mohammad Z., Muzamil J., Rashid A.* (SMHS Hospital, Government Medical College). Ireland: Aremu M.*, Canas-Martinez A., Cullivan O., Murphy C., Owens P., Pickett L. (Connolly Hospital Blanchardstown); Corrigan M.*, Daly A., Fleming C.*, Jordan P., Killeen S., Lynch N., O'Brien S., Syed W. A. S., Vernon L. (Cork University Hospital); Fahey B. A., Larkin J. O.*, McCormick P., Mehigan B. J., Mohan H., Shokuhi P., Smith. J (St James's Hospital); Bashir Y., Bass G. A., Connelly T. M., Creavin B., Earley H., Elliott J. A.*, Gillis A. E., Kavanagh D. O., Neary P. C., O'Riordan J. M., Reynolds I. S., Rice D., Ridgway P. F., Umair M., Whelan M. (Tallaght University Hospital); Corless K., Finnegan L., Fowler A., Hogan A., Lowery A.*, McKevitt K.*, Ryan É. (University Hospital Galway); Coffey J. C., Cunningham R. M., Devine M., Nally D.*, Peirce C. (University Hospital Limerick); Hardy N. P., Neary P. M., O'Malley S.*, Ryan M. (University Hospital Waterford/University College Cork). Italy: Macina S.* (ASST Mantua); Mariani N. M.*, Opocher E., Pisani Ceretti A. (ASST Santi Paolo E. Carlo); Bianco F.* (ASST Papa Giovanni XXIII – Bergamo); Marino M. V.*, Mirabella A., Vaccarella G. (Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello); Agostini C., Alemanno G., Bartolini I., Bergamini C., Bruscino A., De Vincenti R., Di Bella A., Fortuna L., Maltinti G., Muiesan P.*, Prosperi P.*, Ringressi M. N., Risaliti M., Taddei A.*, Tucci R. (Azienda Ospedaliera Universitaria Careggi); Campagnaro T.*, Guglielmi A., Pedrazzani C., Rattizzato S., Ruzzenente A., Turri G. (Azienda Ospedaliera Universitaria Integrata di Verona); Bellora P., D'Aloisio G., Ferrari M., Francone E., Gentilli S.*, Nikaj H. (Azienda Ospedaliero Universitaria Maggiore della Carità); Bianchini M., Chiarugi M., Coccolini F., Di Franco G., Furbetta N., Gianardi D., Guadagni S., Morelli L.*, Palmeri M., Tartaglia D.* (Azienda Ospedaliero Universitaria Pisana); Anania G.*, Carcoforo P.*, Chiozza M., De Troia A., Koleva Radica M., Portinari M., Sibilla M. G., Urbani A. (Azienda Ospedaliero Universitaria San'anna); Fabbri N., Feo C. V.*, Gennari S., Parini S., Righini E. (Azienda Unità Sanitaria Locale di Ferrara, Università di Ferrara); Annessi V., Castro Ruiz C., Montella M. T., Zizzo M.* (Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia); Grossi U., Novello S., Romano M., Rossi S., Zanus G.* (Ca' Foncello Treviso – DISCOG – Università di Padova); Esposito G., Frongia F., Pisanu A., Podda M.* (Cagliari University Hospital); Belluco C., Lauretta A.*, Montori G., Moras L., Olivieri M.; Feo C. F., Perra T.*, Porcu A.*, Scanu A. M. (Cliniche San Pietro, Aou Sassari); Aversano A., Carbone F., Delrio P.*, Di Lauro K., Fares Bucci A., Rega D.*, Spiezio G. (Colorectal Surgical Oncology Unit – Istituto Nazionale Tumori Fondazione, Pascale IRCCS); Calabrò M.*, Farnesi F., Lunghi E. G., Muratore A.*, Pipitone Federico N. S. (Edoardo Agnelli); De Palma G. D., Luglio G.*, Pagano G., Tropeano F. P. (Federico II University Hospital); Baldari L.*, Boni L.*, Cassinotti E.* (Fondazione IRCCS Ca' Granda – Ospedale Maggiore Policlinico di Milano); Cosimelli M., Fiore M.*, Guaglio M.*, Sorrentino L. (Fondazione IRCCS Istituto Nazionale dei Tumori, Milano); Agnes A., Alfieri S., Belia F., Biondi A., Cozza V., D'Ugo D., De Simone V., Litta F., Lorenzon L., Marra A. A., Marzi F., Parello A., Persiani R., Ratto C., Rosa F., Scrima O., Sganga G. (Fondazione Policlinico Universitario Agostino Gemelli IRCCS); Belli A.*, Izzo F., Patrone R. (HPB Surgical Oncology Unit – Istituto Nazionale Tumori Fondazione, Pascale IRCCS); Carrano F. M., Carvello M. M., Di Candido F., Maroli A., Spinelli A.* (Humanitas Clinical and Research Center IRCCS, Rozzano (Mi) and Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (Mi)); Aprile A., Batistotti P., Massobrio A., Pertile D., Scabini S.*, Soriero D. (IRCCS Ospedale Policlinico San Martino); De Manzoni Garberini A.* (Ospedale Civile Spirito Santo); Federico P., Maida P., Marra E., Marte G., Petrillo A., Tammaro P., Tufo A.* (Ospedale del Mare); Berselli M.*, Borroni G.*, Cocozza E., Conti L., Desio M., Rizzi A. (ASST Sette Laghi-Varese); Baldi C.*, Corbellini C., Sampietro G. M. (Ospedale di Rho – ASST Rhodense); Baldini E.*, Capelli P., Conti L., Isolani S. M., Ribolla M. (Ospedale Guglielmo da Saliceto Piacenza); Bondurri A., Colombo F.*, Ferrario L., Guerci C., Maffioli A. (Ospedale Luigi Sacco Milano); Armao T., Ballabio M.*, Bisagni P., Gagliano A., Longhi M., Madonini M., Pizzini P. (Ospedale Maggiore di Lodi); Mochet S.*, Usai A. (Ospedale Regionale Umberto Parini); Bianco F.*, Incollingo P. (Ospedale S. Leonardo – Asl Napoli 3 Sud, Castellammare di Stabia); Mancini S., Marino Cosentino L.*, Sagnotta A.* (Ospedale San Filippo Neri); Nespoli L. C., Tamini N.* (Ospedale San Gerardo); Anastasi A., Bartalucci B., Bellacci A., Canonico G.*, Capezzuoli L., Di Martino C., Ipponi P., Linari C., Montelatici M., Nelli T., Spagni G., Tirloni L., Vitali A. (Ospedale San Giovanni di Dio); Abate E., Casati M.*, Casiraghi T., Laface L., Schiavo M. (Ospedale Vittorio Emanuele III – Carate Brianza); Arminio A., Cotoia A., Lizzi V.*, Vovola F. (Ospedali Riuniti Azienda Ospedaliera Universitaria Foggia); Vergari R.* (Ospedali Riuniti di Ancona); D'Ugo S.*, Depalma N., Spampinato M. G. (Vito Fazzi, Leece); Brachini G., Chiappini A., Cicerchia P. M., Cirillo B., De Toma G., Fiori E., Fonsi G. B., Iannone I., La Torre F., Lapolla P.*, Meneghini S., Mingoli A., Sapienza P., Zambon M. (Policlinico Umberto I Sapienza University of Rome); Capolupo G. T.*, Mazzotta E. (Policlinico Universitario Campus Bio Medico of Rome); Gattolin A., Migliore M., Rimonda R., Sasia D.*, Travaglio E. (Regina Montis Regalis Hospital, Mondovì); Cervellera M., Gori A., Sartarelli L., Tonini V.* (S. Orsola-Malpighi Hospital); Chessa A.*, Fiorini A., Norcini C. (San Giovanni di Dio); Colletti G., Confalonieri M., Costanzi A.*, Frattaruolo C., Mari G., Monteleone M. (San Leopoldo Mandic); De Nardi P.*, Parise P., Vignali A. (San Raffaele Scientific Institute, Milan); Belvedere A., Bernante P., Jovine E., Neri J., Parlanti D., Pezzuto A. P., Poggioli G., Rottoli M.*, Tanzanu M., Violante T. (IRCCS Azienda Ospedaliero – Universitaria di Bologna; Alma Mater Studiorum University of Bologna); Borghi F., Cianflocca D., Di Maria Grimaldi S., Donati D., Gelarda E., Giraudo G., Giuffrida M. C., Marano A.*, Palagi S., Pellegrino L., Peluso C., Testa V.* (Santa Croce E. Carle Hospital, Cuneo); Agresta F.*, Prando D.*, Zese M.* (Santa Maria degli Angeli Hospital ULSS 5 – Adria); Armatura G.*, Frena A., Scotton G.* (St Moritz Hospital); Gallo G.*, Sammarco G., Vescio G. (University 'Magna Graecia' of Catanzaro); Di Marzo F.* (Valtiberina); Fontana T.* ('Vittorio Emanuele' – Gela). Japan: Kanemitsu Y.*, Moritani K. (National Cancer Center Hospital). Jordan: Al Abdallah M.*, Ayasra F., Ayasra Y., Qasem A. (Al-Basheer Hospital); Fahmawee T., Hmedat A., Obeidat K.* (King Abdullah University Hospital); Abou Chaar M. K., Al-Masri M.*, Al-Najjar H., Alawneh F. (King Hussein Cancer Center). Libya: Alkadeeki G.*, Al Maadany F. S. (Al-Jalaa Hospital); Aldokali N., Senossi O., Subhi M. T. (Alkhadra Hospital); Burgan D.*, Kamoka E., Kilani A. I. (National Cancer Institute, Sabratha); Ellojli I.*, Kredan A. (Tripoli University Hospital). Lithuania: Bradulskis S., Dainius E., Kubiliute E., Kutkevičius J., Parseliunas A., Subocius A., Venskutonis D.* (Lithuanian University of Health Sciences Kaunas Clinical Hospital). Madagascar: Rasoaherinomenjanahary F.*, Razafindrahita J. B., Samison L. H. (Joseph Ravoahangy Andrianavalona Hospital). Malaysia: Hamdan K. H., Ibrahim M. R., Tan J. A., Thanapal M. R.* (Hospital Kuala Lumpur); Amin Sahid N., Hayati F.*, Jayasilan J., Sriram R. K.*, Subramaniam S. (Queen Elizabeth Hospital and Universiti Malaysia Sabah, Kota Kinabalu, Sabah); Che Jusoh M. A., Hussain A. H., Mohamed Sidek A. S., Mohd Yunus M. F., Soh J. Y., Wong M., Zakaria A. D.*, Zakaria Z. (School of Medical Sciences and Hospital, Universiti Sains Malaysia); Fathi N. Q., Xavier R. G., Roslani A. C.* (University Malaya Medical Centre). Mexico: Buerba G. A., Mercado M. Á.*, Posadas-Trujillo O. E., Salgado-Nesme N., Sarre C. (Instituto Nacional de Ciencias Médicas y Nutrición 'Salvador Zubirán'). Morocco: Amrani L., El Ahmadi B., El Bouazizi Y., Majbar A. M., Benkabbou A., Mohsine R., Souadka A.* (Institut National d'Oncologie, Université Mohammed V Rabat). Netherlands: Hompes R.*, Meima-van Praag E. M., Pronk A. J. M., Sharabiany S. (Amsterdam UMC, University of Amsterdam); Grotenhuis B.*, Hartveld L. (Antoni Van Leeuwenhoek Ziekenhuis); Posma-Bouman L.* (Slingeland Ziekenhuis); Derksen T., Franken J., Oosterling S.* (Spaarne Gasthuis); Konsten J.*, Van Heinsbergen M. (Viecuri Medisch Centrum). Nigeria: Olaogun J.* (Ekiti State University Teaching Hospital); Abdur-Rahman L.*, Adeyeye A.*, Bello J., Olasehinde O., Popoola A. (University of Ilorin Teaching Hospital). Pakistan: Jamal A., Kerawala A. A.* (Cancer Foundation Hospital); Memon A. S.*, Nafees Ahmed R., Rai .L* (Dr Ruth K. M. Pfau Civil Hospital); Ayub B., Ramesh P., Sayyed R.* (Patel Hospital); Butt U. I.*, Kashif M., Qureshi A.*, Farooka M. W.*, Ayyaz M.* (Services Hospital Lahore); Ayubi A., Waqar S. H.* (Pakistan Institute of Medical Sciences). Poland: Major P. (Jagiellonian University Medical College). Portugal: Azevedo C., Machado D., Mendes F.* (Centro Hospitalar Cova da Beira); De Sousa X.* (Centro Hospitalar de Setúbal); Fernandes U., Ferreira C.*, Guidi G., Marçal A., Marques R., Martins D., Vaz Pereira R., Vieira B. (Centro Hospitalar de Trás-Os-Montes e Alto Douro, EPE); Afonso J., Almeida J. I., Almeida-Reis R.*, Correia de Sá T., Costa M. J. M. A., Fernandes V., Ferraz I., Lima da Silva C., Lopes L., Machado N., Marialva J., Nunes Coelho M., Pereira C., Ribeiro A., Ribeiro C. G., Santos R., Saraiva P., Silva R., Tavares F., Teixeira M. (Centro Hospitalar do Tamega e Sousa); Almeida A. C., Amaral M. J., Andrade R., Camacho C., Costa M., Lázaro A.*, Nogueira O., Oliveira A., Ruivo A., Silva M., Simões J. (Centro Hospitalar e Universitário de Coimbra); Devezas V., Jácome F., Nogueiro J., Pereira A., Santos-Sousa H.*, Vaz S. (Centro Hospitalar e Universitário de São João); Pinto J., Tojal A.* (Centro Hospitalar Tondela-Viseu); Cardoso P.*, Cardoso N., Domingos J. C., Henriques P., Manso M. I., Martins dos Santos G., Martins R., Morais H.*, Pereira R., Revez T., Ribeiro R., Ribeiro V. I., Soares A. P., Sousa S., Teixeira J. (Centro Hospitalar Universitário do Algarve – Unidade de Faro); Amorim E., Baptista V. H., Cunha M. F.*, Sampaio da Nóvoa Gomes Miguel I. I. (Centro Hospitalar Universitário do Algarve – Unidade de Portimão); Bandovas J. P., Borges N.*, Chumbinho B., Figueiredo de Barros I., Frade S., Gomes J., Kam da Silva Andrade A., Pereira Rodrigues A., Pina S., Silva N.*, Silveira Nunes I., Sousa R. (Centro Hospitalar Universitário Lisboa Central); Azevedo P., Costeira B., Cunha C., Garrido R.*, Miranda P., Peralta Ferreira M., Sousa Fernandes M. (Hospital Beatriz Angelo); Galvão D., Vieira A.* (Hospital de Santo Espirito da Ilha Terceira); Patrício B., Santos P. M. D. D.*, Vieira Paiva Lopes A. C. (Hospital de Torres Vedras – Centro Hospitalar do Oeste); Cunha R., Faustino A., Freitas A., Mendes J. R.*, Parreira R. (Hospital do Divino Espírito Santo); Abreu da Silva A.*, Claro M., Costa Santos D., Deus A. C., Grilo J. V. (Hospital do Litoral Alentejano); Borges F.*, Corte Real J., Henriques S., Lima M. J., Matos Costa P. (Hospital Garcia de Orta); Brito da Silva F., Caiado A.*, Fonseca F. (Instituto Português de Oncologia de Lisboa Francisco Gentil); Ângelo M., Baiao J. M., Martins Jordão D.*, Vieira Caroço T. (IPO Coimbra); Baía C., Canotilho R., Correia A. M., Ferreira Pinto A. P., Peyroteo M., Videira J. F.* (IPO Porto). Réunion: Kassir R.*, Sauvat F. (CHU Réunion). Romania: Bezede C., Chitul A., Ciofic E., Cristian D., Grama F.* (Coltea Clinical Hospital); Bonci E.*, Gata V.*, Titu S.* (Prof. Dr. Ion Chiricuta Institute of Oncology). Russia: Garmanova T., Kazachenko E., Markaryan D., Rodimov S., Tsarkov P.*, Tulina I. (Clinic of Coloproctology and Minimally Invasive Surgery, Sechenov Medical State University); Litvina Y., Provozina A. (Immanuel Kant Baltic Federal University, Regional Clinical Hospital); Agapov M.*, Galliamov E., Kakotkin V., Kubyshkin V., Kamalov A., Semina E. (Moscow Research and Educational Center, Lomonosov Moscow State University). Saudi Arabia: Alshahrani M.*, Alsharif F., Eskander M. (Aseer Central Hospital); Alharthi M., Aljiffry M., Basendowah M., Malibary N.*, Nassif M., Saleem A., Samkari A., Trabulsi N.* (King Abdulaziz University Hospital); Al Awwad S.*, Alghamdi M.*, Alnumani T.* (King Fahad General Hospital); Al Habes H., Alqannas M.*, Alyami M.*, Alzamanan M., Cortés Guiral D.*, Elawad A. (King Khalid Hospital); AlAamer O., Alselaim N.* (King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Ministry of National Guard, Health Affairs, General Surgery Department); Al-Khayal K., Alhassan N., Alobeed O., Alshammari S., Bin Nasser A.*, Bin Traiki T., Nouh T.*, Zubaidi A. M. (King Saud University). Serbia: Aleksić L., Antic A., Barisic G.*, Ceranic M., Grubač Ž., Jelenkovic J., Kecmanović D., Kmezić S., Knezevic D.*, Krivokapic Z.*, Latinčić S., Markovic V.*, Matić S.*, Miladinov M., Pavlov M.*, Pejovic I., Tadic B., Vasljević J., Velickovic D. (Clinic for Digestive Surgery, Clinical Centre of Serbia); Buta M., Cvetkovic A., Gacic S., Goran M., Jeftic N., Markovic I.*, Milanović M., Nikolic S., Pejnovic L., Savković N., Stevic D., Vucic N., Zegarac M. (Institute for Oncology and Radiology of Serbia); Karamarkovic A., Kenic M., Kovacevic B., Krdzic I.* (Zvezdara University Medical Center). Singapore: Lieske B.* (National University Hospital). South Africa: Almgla N.*, Boutall A., Herman A., Kloppers C.*, Nel D., Rayamajhi S. (Groote Schuur Hospital). Spain: Paniagua García Señorans M.*, Vigorita V. (Álvaro Cunqueiro Hospital); Acrich E., Baena Sanfeliu E., Barrios O., Golda T.*, Santanach C., Serrano-Navidad M., Sorribas Grifell M., Vives R. V. (Bellvitge University Hospital); Escolà D., Jiménez A.* (Comarcal Alt Penedés); Cayetano Paniagua L., Gómez Fernández L.* (Consorci Sanitari de Terrassa); Collera P., Diaz Del Gobbo R., Farre Font R., Flores Clotet R., Gómez Díaz C. J.*, Guàrdia N., Guariglia C. A., Osorio A., Sanchez Jimenez R., Sanchon L., Soto Montesinos C. (Fundació Althaia – Xarxa Assistencial Universitària de Manresa); Alonso-Lamberti L., García-Quijada J., Jimenez Miramón J., Jimenez V.*, Jover J. M., Leon R., Rodriguez J. L., Salazar A., Valle Rubio A. (Getafe University Hospital); Aguado H.* (Hellín Hospital); Bravo Infante R., De Lacy F. B., Lacy A. M.*, Otero A., Turrado-Rodriguez V.*, Valverde S. (Hospital Clinic Barcelona); Anula R., Cano-Valderrama O., Del Campo Martín M., Díez-Valladares L., Domínguez I., Dziakova J., García Alonso M., García Romero E., Gómez Latorre L., Muguerza J.M.*, Pizarro M. J., Saez Carlin P., Sánchez del Pueblo C., Sánchez-Pernaute A., Sanz Ortega G., Sanz-Lopez R., Torres A. (Hospital Clínico de Madrid); Garcés-Albir M.*, Lopez F.*, Martín-Arévalo J., Moro-Valdezate D.*, Pla Marti V. (Hospital Clínico Universitario de Valencia); Beltrán de Heredia J., De Andrés Asenjo B.*, Gómez Sanz T., Jezieniecki C., Nuñez del Barrio H., Ortiz de Solórzano Aurusa F. J., Romero de Diego A., Ruiz Soriano M., Trujillo Díaz J., Vázquez Fernández A. (Hospital Clínico Universitario de Valladolid); Lora-Cumplido P., Sosa M. V.* (Hospital de Cabueñes); Gonzalez-Gonzalez E., Minaya Bravo A. M.* (Hospital del Henares); Alonso de la Fuente N., Jimenez Toscano M.* (Hospital del Mar); Grau-Talens E. J., Martin-Perez B.* (Hospital Don Benito-Villanueva); Benavides Buleje J. A., Carrasco Prats M.*, Giménez Francés C.*, Muñoz Camarena J. M., Parra Baños P. A., Peña Ros E., Ramirez Faraco M., Ruiz-Marín M.*, Valero Soriano M. (Hospital General Reina Sofía); Estaire Gómez M.*, Fernández Camuñas Á., Garcia Santos E. P., Jimenez Higuera E., Martínez-Pinedo C., Muñoz-Atienza V., Padilla-Valverde D.*, Picón Rodríguez R., Sánchez-García S., Sanchez-Pelaez D. (Hospital General Universitario de Ciudad Real); Colombari R. C., del Valle E., Fernández M., Lozano Lominchar P.*, Martín L., Rey Valcarcel C., Zorrilla Ortúzar J. (Hospital General Universitario Gregorio Marañón); Alcaide Matas F., García Pérez J. M., Troncoso Pereira P.* (Hospital Mateu Orfila); Mora-Guzmán I.* (Hospital Santa Bárbara); Achalandabaso Boira M.*, Sales Mallafré R. (Hospital Universitari de Tarragona Joan XXIII); Marín H., Prieto Calvo M., Villalabeitia Ateca I.* (Hospital Universitario Cruces); De Andres Olabarria U., Durán Ballesteros M., Fernández Pablos F. J., Ibáñez-Aguirre F. J., Sanz Larrainzar A., Ugarte-Sierra B.* (Hospital Universitario de Galdakao); Correa Bonito A., Delgado Búrdalo L., Di Martino M.*, García Septiem J.*, Maqueda González R., Martin-Perez E. (Hospital Universitario de la Princesa); Calvo Espino P.*, Guillamot Ruano P. (Hospital Universitario de Móstoles); Colao García L., Díaz Pérez D.*, Esteban Agustí E., Galindo Jara P., Gutierrez Samaniego M.*, Hernandez Bartolome M. A.*, Serrano González J. (Hospital Universitario de Torrejón de Ardoz); Alonso Poza A., Diéguez B., García-Conde M., Hernández-García M., Losada M.* (Hospital Universitario del Sureste); Alvarez E., Chavarrias N., Gegúndez Simón A., Gortázar S., Guevara J., Prieto Nieto M. I., Ramos-Martín P., Rubio-Perez I.*, Saavedra J., Urbieta A. (Hospital Universitario la Paz); Cantalejo Diaz M., De Miguel Ardevines M. D. C., Duque-Mallén V.*, Gascon Ferrer I., González-Nicolás Trébol M. T., Gracia-Roche C., Herrero Lopez M., Martinez German A., Matute M., Sánchez Fuentes N., Sánchez-Rubio M., Santero-Ramirez M. S., Saudí S. (Hospital Universitario Miguel Servet); Blazquez Martin A., Diez Alonso M.*, Hernandez P., Mendoza-Moreno F., Ovejero Merino E., Vera Mansilla C. (Hospital Universitario Principe de Asturias); Acebes García F., Bailón M., Bueno Cañones A. D., Choolani Bhojwani E., Marcos-Santos P., Miguel T., Pacheco Sánchez D., Pérez-Saborido B., Sanchez Gonzalez J., Tejero-Pintor F. J.* (Hospital Universitario Río Hortega); Cano A., Capitan-Morales L., Cintas Catena J., Gomez-Rosado J.*, Oliva Mompean F., Pérez Sánchez M. A., Río Lafuente F. D., Torres Arcos C., Valdes-Hernandez J. (Hospital Universitario Virgen Macarena); Cholewa H., Frasson M., Martínez Chicote C., Sancho-Muriel J.* (Hospital Universitario Y Politécnico la Fe); Abad Gurumeta A., Abad-Motos A., Martínez-Hurtado E., Ripollés-Melchor J.*, Ruiz Escobar A. (Infanta Leonor University Hospital); Cuadrado-García A.*, Garcia-Sancho Tellez L.*, Heras Aznar J.*, Maté P., Ortega Vázquez I.*, Picardo A. L., Rojo López J. A., Sanchez Cabezudo Noguera F.*, Serralta de Colsa D.* (Infanta Sofía University Hospital); Cagigas Fernandez C., Caiña Ruiz R., Gomez Ruiz M., Martínez-Pérez P., Poch C., Santarrufina Martinez S.*, Valbuena Jabares V. (Marqués de Valdecilla University Hospital); Blas Laina J. L., Cros B., Escartin J.*, Garcia Egea J., Nogués A., Talal El-Abur I., Yánez C. (Royo Villanova); Cagigal Ortega E. P., Cervera I., Díaz Peña P., Gonzalez J., Marqueta De Salas M., Perez Gonzalez M.*, Ramos Bonilla A., Rodríguez Gómez L. (Severo Ochoa University Hospital); Blanco-Colino R., Espin-Basany E.*, Pellino G. (Vall d'Hebron University Hospital). Sri Lanka: Arulanantham A., Bandara G. B. K. D., Jayarajah U.*, Ravindrakumar S., Rodrigo V. S. D. (District General Hospital Chilaw); Srishankar S.* (Teaching Hospital Anuradhapura). Sudan Ali Adil A. K. (Al-Rajhi). Sweden: Älgå A.*, Heinius G., Nordberg M., Pieniowski E. (Stockholm South General Hospital); Löfgren N., Rutegård M.* (Umea University Hospital). Switzerland: Arigoni M., Bernasconi M., Christoforidis D.*, Di Giuseppe M., La Regina D., Mongelli F. (Ente Ospedaliero Cantonale); Chevallay M., Dwidar O., Gialamas E., Sauvain M. (Pourtales Neuchatel Hospital); Adamina M.*, Crugnale A. S., Guglielmetti L., Peros G. (Kantonsspital Winterthur). Turkey: Aghayeva A.*, Hamzaoglu I., Sahin I. (Acibadem Altunizade Hospital); Akaydin E., Aliyeva Z., Aytac E., Baca B., Ozben V.*, Ozmen B. B. (Acibadem Atakent Hospital); Arikan A. E.*, Bilgin I. A.*, Kara H., Karahasanoğlu T., Uras C. (Acibadem Maslak Hospital); Dincer H. A., Erol T. (Hacettepe University Hospital); Alhamed A., Ergün S.*, Özçelık M. F., Sanli A. N., Uludağ S. S.*, Velidedeoglu M.*, Zengin A. K. (Istanbul Universty – Cerrahpaşa Medical Faculty); Bozkurt M. A., Kara Y.*, Kocataş A. (Kanuni Sultan Suleyman Training and Research Hospital); Azamat İ. F., Balik E.*, Buğra D., Kulle C. B. (Koç University Medical School); Gözal K., Güler S. A., Köken H., Tatar O. C.*, Utkan N. Z., Yıldırım A., Yüksel E. (Kocaeli University Teaching Hospital); Akin E., Altintoprak F.*, Cakmak G., Çelebi F., Demir H., Dikicier E., Firat N., Gönüllü E., Kamburoğlu M. B., Küçük I. F., Mantoglu B. (Sakarya University Faculty of Medicine); Çolak E.*, Kucuk G. O., Uyanik M. S. (Samsun Training and Research Hospital); Göksoy B.* (Sehit Prof. Dr. İlhan Varank Training and Research Hospital); Bozkurt E., Mihmanli M., Tanal M.*, Yetkin S. G. (Sisli Hamidiye Etfal Training and Research Hospital); Akalin M., Arican C., Avci E. K., Aydin C., Demirli Atıcı S.*, Emiroglu M., Kaya T.*, Kebabçı E., Kilinc G., Kirmizi Y., Öğücü H., Salimoğlu S., Sert İ., Tugmen C., Tuncer K., Uslu G., Yeşilyurt D. (University of Health Sciences Tepecik Training and Research Hospital); Yildiz A.* (Yildirim Beyazit University Yenimahalle Training and Research Hospital). Uganda: Lule H.*, Oguttu B.* (Kampala International University Teaching Hospital). UK: Agilinko J., Ahmeidat A., Bekheit M.*, Cheung L. K., Kamera B. S., Mignot G., Shaikh S.*, Sharma P. (Aberdeen Royal Infirmary); Al-Mohammad A., Ali S., Ashcroft J., Baker O., Coughlin P., Davies R. J.*, Kyriacou H., Mitrofan C. G., Morris A., Raby-Smith W., Rooney S., Singh A., Tan X. S., Townson A., Tweedle E. (Addenbrooke's Hospital); Angelou D., Choynowski M., McAree B.*, McCanny A., Neely D. (Antrim Area Hospital – Northern Health and Social Care Trust); Mosley F.* (Bradford Royal Infirmary); Arrowsmith L.*, Campbell W.* (Causeway Hospital); Grove T., Kontovounisios C., Warren O.* (Chelsea and Westminster Hospital); Clifford R., Eardley N., Krishnan E., Manu N., Martin E., Roy Mahapatra S., Serevina O. L., Smith C., Vimalachandran D.* (Countess of Chester Hospital); Emslie K.*, Labib P.*, Minto G., Natale J., Panahi P., Rogers L.* (Derriford Hospital); Abubakar A.*, Akhter Rahman M. M., Chan E., O'Brien H., Sasapu K.* (Diana Princess of Wales Hospital Grimsby); Ng H. J.* (Dumfries and Galloway Royal Infirmary); Day A.* (East Surrey Hospital); Hunt A., Laskar N.* (East Sussex Healthcare (Conquest Hospital and Eastbourne District General Hospital)); Gupta A.*, Steinke J., Thrumurthy S. (Epsom and St Helier University Hospitals NHS Trust); Massie E., McGivern K., Rutherford D., Wilson M.* (Forth Valley Royal Hospital); Handa S., Kaushal M., Kler A., Patel P.*, Redfern J., Tezas S. (Furness General Hospital); Aawsaj Y., Barry C., Blackwell L., Emerson H., Fisher A.*, Katory M., Mustafa A. (Gateshead Health NHS Foundation Trust); Kretzmer L.*, Lalou L., Manku B., Parwaiz I., Stafford J. (George Eliot Hospital); Abdelkarim M., Asqalan A., Gala T., Ibrahim S., Maw A.*, Mithany R., Morgan R.*, Sundaram Venkatesan G. (Glan Clwyd Hospital); Boulton A. J. (Good Hope Hospital); Hardie C., McNaught C.* (Harrogate District Hospital); Karandikar S.*, Naumann D. (Heartlands Hospital); Ayorinde J., Chase T., Cuming T., Ghanbari A., Humphreys L., Tayeh S.* (Homerton University Hospital); Aboelkassem Ibrahim A., Evans C., Ikram H., Loubani M.*, Nazir S., Robinson A., Sehgal T., Wilkins A. (Hull University Teaching Hospitals NHS Trust); Dixon J.*, Jha M., Thulasiraman S. V., Viswanath Y. K. S.* (James Cook University Hospital); Curl-Roper T., Delimpalta C., Liao C. C. L.*, Velchuru V., Westwood E. (James Paget University NHS Foundation Trust Hospital); Bond-Smith G.*, Mastoridis S., Tebala G. D., Verberne C. (John Radcliffe Hospital); Bhatti M. I., Boyd-Carson H., Elsey E., Gemmill E., Herrod P.*, Jibreel M., Lenzi E., Saafan T., Sapre D., Sian T., Watson N. (King's Mill Hospital); Athanasiou A.*, Burke J., Costigan F., Elkadi H., Johnstone J., Nahm C. (Leeds Teaching Hospitals Trust); Annamalai S., Ashmore C., Kourdouli A. (Leicester Royal Infirmary); Askari A., Cirocchi N., Kudchadkar S., Patel K., Sagar J.*, Talwar R.* (Luton and Dunstable University Hospital); Abdalla M., Ismail O., Newton K., Stylianides N.* (Manchester Royal Infirmary); Aderombi A., Bajomo O., Beatson K., Garrett W.*, Ng V. (Medway Hospital); Al-Habsi R., Divya G S., Keeler B.* (Milton Keynes University Hospital); Egan R., Fabre I., Harries R.*, Li Z., Parkins K., Spencer N., Thompson D. (Morriston Hospital Swansea); Gemmell C., Grieco C., Hunt L.* (Musgrove Park Hospital); Mahmoud Ali F. (Newcastle Upon Tyne Hospitals NHS Foundation Trust.); Seebah K., Shaikh I.*, Sreedharan L., Youssef M.* (Norfolk and Norwich University Hospital); Shah J.* (North Manchester General Hospital); McLarty N., Mills S.*, Shenfine A. (Northumbria NHS Hospital Trust); Sahnan K. (Northwick Park Hospital); Michel M., Patil S., Ravindran S., Sarveswaran J.*, Scott L. (Pinderfields Hospital); Bhangu A.*, Cato L. D., Kamal M., Kulkarni R., Parente A., Saeed S., Vijayan D. (Queen Elizabeth Hospital Birmingham); Kaul S., Khan A. H., Khan F., Mukherjee S.*, Patel M., Sarigul M., Singh S. (Queen's Hospital Romford); Adiamah A., Brewer H., Chowdhury A.*, Evans J., Humes D.*, Jackman J., Koh A., Lewis-Lloyd C., Oyende O., Reilly J., Worku D. (Queens Medical Centre); Bisset C., Moug S. J.* (Royal Alexandra Hospital); Math S., Sarantitis I., Timbrell S., Vitone L.* (Royal Blackburn Hospital); Faulkner G.* (Royal Bolton Hospital); Brixton G., Findlay L., Majkowska A., Manson J.*, Potter R. (Royal Bournemouth Hospital); Bhalla A.*, Chia Z., Daliya P., Grimley E., Malcolm F. L., Theophilidou E. (Royal Derby Hospital); Daniels I. R., Fowler G., Massey L., McDermott F.*, Rajaretnam N. (Royal Devon and Exeter Hospital); Beamish A., Magowan D., Nassa H., Price C., Smith L., Solari F., Tang A. M., Williams G.* (Royal Gwent Hospital); Davies E.*, Hawkin P., Raymond T., Ryska O. (Royal Lancaster Infirmary); Baron R. D.*, Gahunia S., McNicol F.*, Russ J., Szatmary P., Thomas A. (Royal Liverpool University Hospital); Jayasinghe J. D., Knowles C., Ledesma F. S., Minicozzi A.*, Navaratne L., Ramamoorthy R., Sohrabi C., Thaha M.*, Venn M. (Royal London Hospital); Atherton R.*, Brocklehurst M., McAleer J., Parkin E.* (Royal Preston Hospital); Aladeojebi A., Ali M., Gaunt A.* (Royal Stoke University Hospital); Hammer C., Stebbing J. (Royal Surrey County Hospital); Bhasin S., Bodla A. S., Burahee A., Crichton A., Fossett R., Yassin N.* (Royal Wolverhampton NHS Trust); Brown S.*, Lee M., Newman T., Steele C. (Sheffield Teaching Hospital NHS Foundation Trust); Baker A., Konstantinou C., Ramcharan S.*, Wilkin R. J. W. (South Warwickshire NHS Foundation Trust); Lawday S., Lyons A.* (Southmead Hospital); Chung E., Hagger R., Hainsworth A., Karim A., Owen H., Ramwell A., Williams K.* (St George's Hospital); Hall J. (Stepping Hill Hospital); Harris G., Royle T.*, Watson L. J. (Sunderland Royal Hospital); Asaad P., Brown B., Duff S.*, Khan A., Moura F., Wadham B. (The University Hospital of South Manchester); McCluney S., Parmar C.*, Shah S. (The Whittington Hospital); Babar M. S., Goodrum S., Whitmore H. (Torbay and South Devon NHS Trust); Balasubramaniam D.*, Jayasankar B.*, Kapoor S., Ramachandran A. (Tunbridge Wells Hospital); Beech N., Chand M.*, Green L., Kiconco H., McEwen R. (University College London Hospital); Pereca J.* (University Hospital Ayr); Gash K.*, Gourbault L., MacCabe T., Newton C.* (University Hospitals Bristol NHS Foundation Trust); Baig M., Bates H., Dunne N., Khajuria A., Ng V., Sarma D. R., Shortland T., Tewari N.* (University Hospitals Coventry and Warwickshire NHS Trusts); Akhtar M. A.*, Brunt A., McIntyre J., Milne K., Rashid M. M., Sgrò A., Stewart K. E., Turnbull A. (Victoria Hospital Kirkcaldy); Aguilar Gonzalez M.*, Talukder S.* (West Suffolk Hospital); Eskander P., Hanna M., Olivier J.* (Weston General Hospital); Magee C.*, Powell S.* (Wirral University Teaching Hospital); Flindall I., Hanson A., Mahendran V. (Worcestershire Royal Hospital); Green S., Lim M., MacDonald L., Miu V., Onos L., Sheridan K., Young R.* (York Teaching Hospitals NHS Trust); Alam F., Griffiths O., Houlden C., Kolli V. S., Lala A. K., Seymour Z.* (Ysbyty Gwynedd). USA: Haynes A.*, Hill C., Leede E., McElhinney K., Olson K. A., Riley C., Thornhill M. (Dell Seton Medical Center at the University of Texas); Etchill E., Gabre-Kidan A.*, Jenny H., Kent A., Ladd M. R., Long C., Malapati H., Margalit A., Rapaport S., Rose J., Stevens K., Tsai L., Vervoort D., Yesantharao P., Bigelow B. (Johns Hopkins Hospital); Klaristenfeld D.* (Kaiser Permanente San Diego Medical Center); Huynh K. (Kaiser Permanente West Los Angeles); Azam M., Choudhry A.*, Marx W. (SUNY Upstate University Hospital); Abel M. K., Boeck M., Chern H., Kornblith L.*, Nunez-Garcia B., Ozgediz D., Glencer A., Sarin A., Varma M. (University of California, San Francisco (UCSF)); Abbott D., Acher A., Aiken T., Barrett J., Foley E., Schwartz P., Zafar S. N.* (University of Wisconsin); Hawkins A.*, Maiga A. (Vanderbilt University Medical Center).
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. ; BCAC acknowledgements. We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Gillian Dite. ABCS thanks the Blood bank Sanquin, The Netherlands. ABCTB Investigators: Christine Clarke, Deborah Marsh, Rodney Scott, Robert Baxter, Desmond Yip, Jane Carpenter, Alison Davis, Nirmala Pathmanathan, Peter Simpson, J. Dinny Graham, Mythily Sachchithananthan. Samples are made available to researchers on a non-exclusive basis. BBCS thanks Eileen Williams, Elaine Ryder-Mills, Kara Sargus. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Munoz Garzon, Alejandro Novo Dominguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Pena Fernandez, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), Jose Antunez, Maximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigacion Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquin Gonzalez-Carrero and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgard Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. CNIO-BCS thanks Guillermo Pita, Charo Alonso, Nuria alvarez, Pilar Zamora, Primitiva Menendez, the Human Genotyping-CEGEN Unit (CNIO). The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Krober and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tubingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tubingen [[HB], gefordert durch die Deutsche Forschungsgemeinschaft (DFG) im Rahmen der Exzellenzstrategie des Bundes und der Lander - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [YDK, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bruning, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Kirsimari Aaltonen, Irja Erkkila. HUBCS thanks Shamil Gantsev. KARMA and SASBAC thank the Swedish Medical Research Counsel. KBCP thanks Eija Myohanen, Helena Kemilainen. kConFab/AOCS wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow-Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group): Mariarosaria Calvello, Davide Bondavalli, Aliana Guerrieri Gonzaga, Monica Marabelli, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. The MCCS was made possible by the contribution of many people, including the original investigators, the teams that recruited the participants and continue working on follow-up, and the many thousands of Melbourne residents who continue to participate in the study. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines, Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Quebec - Universite Laval Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skilful technical assistance. J.S. is Chair holder of the Canada Research Chair in Oncogenetics. NBHS and SBCGS thank study participants and research staff for their contributions and commitment to the studies. For NHS and NHS2 the study protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. We would like to thank the participants and staff of the NHS and NHS2 for their valuable contributions as well as the following state cancer registries for their help: A.L., A.Z., A.R., C.A., C.O., C.T., D.E., F.L., G.A., I.D., I.L., I.N., I.A., K.Y., L.A., M.E., M.D., M.A., M.I., N.E., N.H., N.J., N.Y., N.C., N.D., O.H., O.K., O.R., P.A., R.I., S.C., T.N., T.X., V.A., W.A., and W.Y. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander, Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. RBCS thanks Jannet Blom, Saskia Pelders, Annette Heemskerk and the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. We acknowledge funding to the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. CIMBA acknowledgments. All the families and clinicians who contribute to the studies; Catherine M. Phelan for her contribution to CIMBA until she passed away on 22 September 2017; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Gillian Dite, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Grikeviius; Drs Janis Eglitis, Anna Krilova and Aivars Stengrevics; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), in particular: Bernard Peissel, Dario Zimbalatti, Daniela Zaffaroni, Alessandra Viel, Giuseppe Giannini Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. Ms. JoEllen Weaver and Dr. Betsy Bove; FPGMX: members of the Cancer Genetics group (IDIS): Marta Santamarina, Miguel Aguado and Olivia Rios; IFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber); We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Melanie Leone, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valerie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study: Coordinating Centre, Service de Genetique, Institut Curie, Paris, France: Muriel Belotti, Ophelie Bertrand, Anne-Marie Birot, Bruno Buecher, Sandrine Caputo, Anais Dupre, Emmanuelle Fourme, Marion Gauthier-Villars, Lisa Golmard, Claude Houdayer, Marine Le Mentec, Virginie Moncoutier, Antoine de Pauw, Claire Saule, Dominique Stoppa-Lyonnet, and Inserm U900, Institut Curie, Paris, France: Fabienne Lesueur, Noura Mebirouk. Contributing Centres: Unite Mixte de Genetique Constitutionnelle des Cancers Frequents, Hospices Civils de Lyon - Centre Leon Berard, Lyon, France: Nadia Boutry-Kryza, Alain Calender, Sophie Giraud, Melanie Leone. Institut Gustave Roussy, Villejuif, France: Brigitte Bressac-de-Paillerets, Olivier Caron, Marine Guillaud-Bataille. Centre Jean Perrin, Clermont-Ferrand, France: Yves-Jean Bignon, Nancy Uhrhammer. Centre Leon Berard, Lyon, France: Valerie Bonadona, Christine Lasset. Centre Francois Baclesse, Caen, France: Pascaline Berthet, Laurent Castera, Dominique Vaur. Institut Paoli Calmettes, Marseille, France: Violaine Bourdon, Catherine Nogues, Tetsuro Noguchi, Cornel Popovici, Audrey Remenieras, Hagay Sobol. CHU Arnaud-de-Villeneuve, Montpellier, France: Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret, Lille, France: Claude Adenis, Aurelie Dumont, Francoise Revillion. Centre Paul Strauss, Strasbourg, France: Daniele Muller. Institut Bergonie, Bordeaux, France: Emmanuelle Barouk-Simonet, Francoise Bonnet, Virginie Bubien, Michel Longy, Nicolas Sevenet, Institut Claudius Regaud, Toulouse, France: Laurence Gladieff, Rosine Guimbaud, Viviane Feillel, Christine Toulas. CHU Grenoble, France: Helene Dreyfus, Christine Dominique Leroux, Magalie Peysselon, Rebischung. CHU Dijon, France: Amandine Baurand, Geoffrey Bertolone, Fanny Coron, Laurence Faivre, Caroline Jacquot, Sarab Lizard. CHU St-Etienne, France: Caroline Kientz, Marine Lebrun, Fabienne Prieur. Hotel Dieu Centre Hospitalier, Chambery, France: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice, France: Veronique Mari. CHU Limoges, France: Laurence Venat-Bouvet. CHU Nantes, France: Stephane Bezieau, Capucine Delnatte. CHU Bretonneau, Tours and Centre Hospitalier de Bourges France: Isabelle Mortemousque. Groupe Hospitalier Pitie-Salpetriere, Paris, France: Chrystelle Colas, Florence Coulet, Florent Soubrier, Mathilde Warcoin. CHU Vandoeuvre-les-Nancy, France: Myriam Bronner, Johanna Sokolowska. CHU Besancon, France: Marie-Agnes Collonge-Rame, Alexandre Damette. CHU Poitiers, Centre Hospitalier d'Angouleme and Centre Hospitalier de Niort, France: Paul Gesta. Centre Hospitalier de La Rochelle: Hakima Lallaoui. CHU Nimes Caremeau, France: Jean Chiesa. CHI Poissy, France: Denise Molina-Gomes. CHU Angers, France: Olivier Ingster; Ilse Coene en Brecht Crombez; Ilse Coene and Brecht Crombez; Alicia Tosar and Paula Diaque; Drs.Sofia Khan, Taru A. Muranen, Carl Blomqvist, Irja Erkkila and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, S. Verhoef, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collee, A.M.W. van den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T. Wijnen, R.A.E.M. Tollenaar, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, R.B. van der Luijt, C.C. van der Pol; Amsterdam Medical Center, NL: C.M. Aalfs, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, NL: E.B. Gomez-Garcia, M.J. Blok; University Medical Center Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen; The Netherlands Comprehensive Cancer Organization (IKNL): S. Siesling, J.Verloop; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Ana Peixoto, Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow-Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Leigha Senter, Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O'Conor; HVH: acknowledgments to the Cellex Foundation for providing research facilities and equipment. Dr Juliette Coignard was supported by a fellowship of INCa Institut National du Cancer N degrees 2015-181, la Ligue Nationale contre le Cancer IP/SC-15229 and Olga Sinilnikova's fellowship (2016). BCAC Funding. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Communitys Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia and acknowledges funding from the National Breast Cancer Foundation (JS). For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The BREast Oncology GAlician Network (BREOGAN) is funded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI12/00070). The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki UniversityHospital Research Fund, the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). G.C.T. and P.W. are supported by the NHMRC. RB was a Cancer Institute NSW Clinical Research Fellow. LMBC is supported by the 'Stichting tegen Kanker'. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC; IG2014 no.15547) to P. Radice. The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414 and 1074383 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program - grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade - grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council (VR 2017-00644) grant for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER). The SZBCS and IHCC were supported by Grant PBZ_KBN_122/P05/2004 and the program of the Minister of Science and Higher Education under the name Regional Initiative of Excellence in 2019-2022 project number 002/RID/2018/19 amount of financing 12 000 000 PLN. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. CIMBA Funding. CIMBA: The CIMBA data management and data analysis were supported by Cancer Research - UK grants C12292/A20861, C12292/A11174. GCT and ABS are NHMRC Research Fellows. iCOGS: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Quebec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BIDMC: Breast Cancer Research Foundation. CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to S. Manoukian. Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo. DEMOKRITOS: European Union (European Social Fund - ESF) and Greek national funds through the Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund. DKFZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: A.K.G. was in part funded by the NCI (R01 CA214545), The University of Kansas Cancer Center Support Grant (P30 CA168524), The Kansas Institute for Precision Medicine (P20 GM130423), and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. is the Chancellors Distinguished Chair in Biomedical Sciences Professorship. A.Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigacion Biomedica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundacion Mutua Madrilena (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association Le cancer du sein, parlons-en! Award, the Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program and the French National Institute of Cancer (INCa grants 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015). GEORGETOWN: the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research, and Swing Fore the Cure. G-FAST: Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HEBON thanks the registration teams of Dutch Cancer Registry (IKNL; S. Siesling, J. Verloop) and the Dutch Pathology database (PALGA; L. Overbeek) for part of the data collection. ICO: The authors would like to particularly acknowledge the support of the Asociacion Espanola Contra el Cancer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economia y Competitividad) and Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563 and CIBERONC) and the Institut Catala de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). INHERIT: Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program - grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade - grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and 5x1000 Istituto Oncologico Veneto grant. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201),and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-00-00171, 18-515-45012 and 19-515-25001). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumours (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UPENN: Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. HVH: Supported by the Carlos III National Health Institute funded by FEDER funds - a way to build Europe - PI16/11363. MT Parsons is supported by a grant from Newcastle University. Kelly-Anne Phillips is an Australian National Breast Cancer Foundation Fellow. ; Sí
Publisher's version (útgefin grein) ; Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors. ; Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the "Fondo Europeo de Desarrollo Regional, una manera de hacer Europa" (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. BCAC: we thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Tu Nguyen-Dumont is a National Breast Cancer Foundation (Australia) Career Development Fellow. ABCS thanks the Blood bank Sanquin, The Netherlands. Samples are made available to researchers on a non-exclusive basis. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. Hedy Rennert, Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Muñoz Garzón, Alejandro Novo Domínguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Peña Fernández, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), José Antúnez, Máximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigación Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquín González-Carreró and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. Investigators from the CPS-II cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Kröber and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nüchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Heidi Toiminen, Kristiina Aittomäki, Irja Erkkilä and Outi Malkavaara. HMBCS thanks Peter Hillemanns, Hans Christiansen and Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myöhänen, Helena Kemiläinen. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB "Georgi D. Efremov), Katerina Kubelka, Mitko Karadjozov (Adzibadem-Sistina" Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika" Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group) thanks Daniela Zaffaroni, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines and Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thanks study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses' Health Study and Nurses' Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The study protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander and Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CIMBA: we are grateful to all the families and clinicians who contribute to the studies; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Griškevičius; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), thanks in particular: Giulia Cagnoli, Roberta Villa, Irene Feroce, Mariarosaria Calvello, Riccardo Dolcetti, Giuseppe Giannini, Laura Papi, Gabriele Lorenzo Capone, Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato, Isabella Marchi, Elena Bandieri, Antonio Russo, Daniele Calistri and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. FPGMX: members of the Cancer Genetics group (IDIS): Ana Blanco, Miguel Aguado, Uxía Esperón and Belinda Rodríguez. We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Diana Torres, Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Mélanie Léoné, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valérie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study. Drs.Sofia Khan, Irja Erkkilä and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C.M. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): A.W. van den Belt-Dusebout. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Overbeek; the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Aniko Bozsik, Zoltan Matrai, Miklos Kasler, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clinicians and patients for their contributions to this study; HVH (University Hospital Vall d'Hebron) the authors acknowledge the Oncogenetics Group (VHIO) and the High Risk and Cancer Prevention Unit of the University Hospital Vall d'Hebron, Miguel Servet Progam (CP10/00617), and the Cellex Foundation for providing research facilities and equipment; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab investigators, research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O'Conor; Christina Selkirk; Helena Jernström, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna Öfverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellström Pigg, Richard Rosenquist; from Linköping University Hospital: Marie Stenmark-Askmalm, Sigrun Liedgren; Cecilia Zvocec, Qun Niu; Joyce Seldon and Lorna Kwan; Dr. Robert Nussbaum, Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad and Salina Chan; Carole Pye, Patricia Harrington and Eva Wozniak. OSUCCG thanks Kevin Sweet, Caroline Craven, Julia Cooper, Michelle O'Conor and Amber Aeilts. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l'Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BCINIS study was funded by the BCRF (The Breast Cancer Research Foundation, USA). The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the German Research Foundation (Do 761/10-1). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. E.K was supported by the program for support the bioresource collections №007-030164/2 and study was performed as part of the assignment of the Ministry of Science and Higher Education of Russian Federation (№АААА-А16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. LMBC is supported by the 'Stichting tegen Kanker'. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov" and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 × 1000"). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council [grant 2017-00644 for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER)]. The SZBCS is financially supported under the program of Minister of Science and Higher Education "Regional Initiative of Excellence" in years 2019-2022, Grant No 002/RID/2018/19. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. CIMBA CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015 and Nr. P-MIP-19-164. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Funds from Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5 × 1000') to S. Manoukian. UNIROMA1: Italian Association for Cancer Research (AIRC; grant no. 21389) to L. Ottini. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: NIH/NCI grant P30-CA006927. The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. Ana Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, the French National Institute of Cancer (INCa) (grants AOR 01 082, 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015) and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). GEORGETOWN: the Survey, Recruitment and Biospecimen Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008) and the Fisher Center for Hereditary Cancer and Clinical Genomics Research. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. HVH (University Hospital Vall d'Hebron) This work was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds: FIS PI12/02585 and PI15/00355. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and "Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa" (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, P18/01029, and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338, 2017SGR449, and PERIS Project MedPerCan), and CERCA program. IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and "5 × 1000" Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-45012). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: was funded by the Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Researc h UK. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. ; Peer Reviewed
In the present essay, I will examine the traces of coexistence between the Muslim and Christian world in architecture and literature, using the examples of the mezquita, or 'mosque', and the most important novel of Spain, Don Quixote of la Mancha (1605;1615) by Miguel de Cervantes Saavedra. This study incorporates an interdisciplinary approach that utilizes historical, literary, and architectural methods to explain the dual function of the margin— its architectural function in the Mosque and its narrative function as used in specific chapters from Cervantes's novel. Furthermore, I will show how the architectural margin of the wall of the mosque was familiar to Cervantes's readers who lived in Spain and this familiarity allows Cervantes to exploit the metaphorical meaning of the literary margin as architectural margin. A metaphor establishes an equivalency between a pair of images; the best-known example of which belongs to Ezra Pound, the founding leader of Imagism (1912-1923). This is a school of poetry that endorsed clarity of expression and simplicity through the use of precise visual imagery. The best known metaphor is Pound's own, in which faces are compared with petals in the poem, "In a Station of the Metro": The apparition of these faces in the crowd: Petals on a wet, black bough. Through his architectural and literary metaphor, Cervantes covertly expresses his personal beliefs about multiculturalism that could not be directly expressed for fear of censorship by the Inquisition. ; Winner of the 2020 Friends of the Kreitzberg Library Award for Outstanding Research in the Senior Arts/Humanities category. ; In the Margins of Literary and Architectural Discourse: A Comparison of Arabic Commentary in Cervantes's Don Quixote and Moorish Architectural Inscription Pablo Picasso: Don Quixote, August 10, 1955. Internet: Public Domain Alexandra Parent SP 415: Seminar on Don Quixote Professor Stallings-Ward 28 February 2020 1 Introduction The history of the Iberian Peninsula is a rich one, filled with influences from the entire European and Asian continents over time. When we think about Spain, there is one defining factor that distinguishes her from the rest of Europe: the presence of racial, ethnic and religious influence from Africa, and, resulting therefrom, a unique moment in world history: the confluence of three major world religions in one geographical place. Christianity, Judaism, and Islam once flourished side by side in mutual tolerance and economic interdependence in the Andalusian region of southern Spain, known as 'Al-Andalus,' in the High Middle Ages. Tolerance of others who are different, as Maria Rosa Menocal points out, is the underpinning of this unique historical coincidence and the essential component for the development of science, philosophy, medicine, urbanization, and hence trade and commercial prosperity.1 The Jews and Christians of Muslim Andalusia flourished economically and culturally under the Umayyad, whose dynasty (661-750) was transplanted from Damascus to Cordoba by Abd al-Rahman (756- 1031) after a civil war between two rival Caliphates. These three religions borrowed language and architecture from one another leaving traces of their coexistence, not surprisingly, within the architecture and literature of Spain. In the present essay, I will examine the traces of coexistence between the Muslim and Christian world in architecture and literature, using the examples of the mezquita, or 'mosque', and the most important novel of Spain, Don Quixote of la Mancha (1605;1615) by Miguel de Cervantes Saavedra. This study incorporates an interdisciplinary approach that utilizes historical, literary, and architectural methods to explain the dual function of the margin— its architectural function in the Mosque and its narrative function as used in specific chapters from Cervantes's 1 Menocal, The Ornament of the World. 2 novel. Furthermore, I will show how the architectural margin of the wall of the mosque was familiar to Cervantes's readers who lived in Spain and this familiarity allows Cervantes to exploit the metaphorical meaning of the literary margin as architectural margin. A metaphor establishes an equivalency between a pair of images; the best-known example of which belongs to Ezra Pound, the founding leader of Imagism (1912-1923). This is a school of poetry that endorsed clarity of expression and simplicity through the use of precise visual imagery. The best- known metaphor is Pound's own, in which faces are compared with petals in the poem, "In a Station of the Metro": The apparition of these faces in the crowd: Petals on a wet, black bough.2 Through his architectural and literary metaphor, Cervantes covertly expresses his personal beliefs about multiculturalism that could not be directly expressed for fear of censorship by the Inquisition. My essay is divided in three sections. In the first section, I will present a historical overview of Muslim presence in the Iberian Peninsula. In the second section, I present a survey of Muslim Architecture in Andalusia based on the results of a photographic study of architecture I did while visiting Spain during study abroad. I survey the presence of Muslim architecture found throughout Andalusia, placing particular emphasis on the function of the margin in the design of the walls of the mosque reserved for the calligraphy that features citations of scripture from the Holy Koran. The margin, although small in size compared to the rest of the entire structure of the mosque, is as I will show, actually the most important part of the mosque. In the third section of my essay, I analyze the literary margin treated in the episode of the lost manuscript in Volume I: Chapters Eight and Nine of Cervantes's Don Quixote. I will look at 2 Judith Stallings-Ward, Gerardo Diego´s Creation Myth of Music: Fábula de Equis y Zeda. London: Routledge, 2020, 175. 3 the coexistence of the Christian and Arab writers in Cervantes's Don Quixote. The collaboration between Cervantes and Cide Hamete Benengeli allows Cervantes to establish a metaphor between the architectural margin of the mosque and the literary margin of the manuscript as the place for covertly expressing his esteem for multiculturalism and his condemnation of the expulsion of the Moors by national decree; a ploy he uses to escape censorship by the Inquisition. The play with spatial perspective (margin vs center) and the severance of the manuscript (with the lost section recovered in the market of Toledo) establishes the architectural and narrative metaphor that recalls the physical and cultural coexistence between Muslims and Christians valued by Cervantes. In addition, I examine how Cervantes extends this metaphor to also evoke the rupture of that coexistence through expulsion of the Moors, which Cervantes believed broke the backbone of the country. Part I: Historical Overview of Muslim Presence in the Iberian Peninsula The invasion of the Iberian Peninsula began with one young man named Abd Al- Rahman, the son of the Arab family ruling Damascus in the east—the Umayyads. However, during a civil war, his family was massacred, and his escape left him the sole survivor. He fled through North Africa into Cordoba where he began to establish himself as the Caliph, or ruler.3 After the Visigoth monarchy fell, Muslim control dominated the Iberian Peninsula. From 711 through 1492, Islamic society had a long and profound presence on shaping Spanish culture until the Christian kings unified the country. By 716, almost all of Iberia, with the exception of the far northwest and mountainous regions, was under Muslim control and the province was name 'Al- Andalus'. By naming the country in this manner, it directly opposes the 'Hispania' title that the 3 BBC Worldwide Learning, The Moorish South: Art in Muslim and Christian Spain from 711-1492. 4 Romans gave the peninsula, foreshadowing the enmity between the religions of Islam and Christianity.4 Abd Al-Rahman sought to recreate his cultural roots here in Iberia. The peninsula was dominated by the Umayyad dynasty, who had no affiliation to the eastern Muslim dynasties at the time, and were met with little to no resistance from the small groups of Christians still living in the peninsula. As demonstrated in Figure 1, the conquering forces came through Northern Africa and thus were also comprised of Berber forces from that region. By 741, there were approximately 12,000 Berber forces, 18,000 Arabs, and 7,000 Syrians entering through the Southern tip of the peninsula. This totaled anywhere from 4,000,000 to 8,000,000 living in the Iberian Peninsula at the time.5 6 Islam and Christianity under Islamic Rule By the mid eighth century, the population of Iberia had grown exponentially and became more diverse both racially and religiously. Although Muslim forces had conquered what remained of the Visigoth territories and established themselves as the dominant, ruling power, a 4 O'Callaghan, A History of Medieval Spain, 91. 5 Phillips and Phillips, A Concise History of Spain. 6 Alchetron.com. "Umayyad Conquest of Hispania - Alchetron, the Free Social Encyclopedia," August 18, 2017. https://alchetron.com/Umayyad-conquest-of-Hispania. Figure 1: Depiction of the route of Abd-Al Rahman and the subsequent conquests of the Muslim Empire. From Internet: public domain.6 5 majority of the population living in Iberia was still Christian. This undoubtedly posed issues for the Moorish rulers who practiced Islam. As a result, conversion became a necessity for Christians. It is important to distinguish between the upper and lower class when discussing the notion of conversion. Many Visigoth royalty, nobles, and influential families saw it in their best interest to convert and to do what they could to join the new rulers in an effort to pursue political advantages.7 Yet, the majority of Iberia was home to lower class Hispano-Roman Christians who converted out of survival. Despite this, many of the people in this situation retained their Christian faith while adopting Muslim customs like learning Arabic so as to appease the rulers. The name given to these people are mozárabes, or 'Mozarabs', meaning 'Muslim-like'.8 A Christian writer noted the following about Christians living under Islamic rule in 854: Our Christian young men, with their elegant airs and fluent speech, are showy in their dress and carriage, and are famed for the learning of the gentiles; intoxicated with Arab eloquence they greedily handle, eagerly devour, and zealously discuss the books of the Chaldeans (i.e. Muhammadans), and make them known by praising them with every flourish of rhetoric, knowing nothing of the beauty of the Church's literature, and looking down with contempt on the streams of the Church that flow forth from Paradise ; alas ! The Christians are so ignorant of their own law, the Latins pay so little attention to their own language, that in the whole Christian flock there is hardly one man in a thousand who can write a letter to inquire after a friend's health intelligibly, while you may find a countless rabble of kinds of them who can learnedly roll out the grandiloquent periods of the Chaldean tongue. They can even make poems, every line ending with the same letter, which displays high flights of beauty and more skill in handling metre than the gentiles themselves possess.9 It is evident from this passage that the Christians admired the Arabs for the type of civilization they created. The Mozarabs recognized that the Arabs had something to offer them in terms of literature, character, and even language. This demonstrates that on some level, there was an 7 Phillips and Phillips, A Concise History of Spain. 8 Phillips and Phillips. 9 Alvar, Indiculus luminosus; quoted from Arnold, The Preaching of Islam; A History of the Propagation of the Muslim Faith, 137-138. 6 acceptance of Muslim culture and practices which set the foundation for the incorporation of Islamic architectural styles and writing styles to be continued after the Christians' reconquering of Iberia. Christian Kingdoms and "La Reconquista" When the Muslim forces conquered Iberia, they were not able to infiltrate the regions in the north. These regions were not seen as an apparent threat because they were isolated, poor, and not heavily populated, so the Moors did not make a vigilant effort to convert or control these Christians.10 However, the Christian states organized themselves into kingdoms and solidified their control in northern Spain by the mid-twelfth century before moving into Southern Spain during the fourteenth and fifteenth centuries. The progression of the Christian kingdoms' conquests can be seen in Figure 2. 11 At the height of the reconquest, there were seven individual Christian kingdoms within the peninsula: Asturias, Galicia, Aragon, Navarre, Leon, Castile, and Valencia. Each of these kingdoms had their own struggles trying to gain territory, power, and recognition. The Kingdom 10 Phillips and Phillips, A Concise History of Spain, 55. 11 "Reconquista+General.Jpg (1600×914)." Accessed February 19, 2020. http://4.bp.blogspot.com/- ofiGywz891k/TzynBPnsc7I/AAAAAAAAAok/ECNzH3rSp3E/s1600/Reconquista+General.jpg. Figure 2: Timeline of the Christian King's Reconquest of the Iberian Peninsula. Internet: public domain.11 7 of Navarre was largely under the control of the French to the north and did not have much to do with the conquering of other Spanish Christian kingdoms, let alone taking a stance on combating the Arab south. However, not only were the Christian kings working to overthrow the Islamic caliphate and reconquer Iberia from the Muslims, they were all vying for control amongst themselves. In the tenth century, Alfonso III expanded into the regions of Galicia and Leon slowly gaining more territory and strengthening his Christian kingdom to combat the Moors. The kingdoms of Castile and Leon unified in 1085 and then under the kingship of Alfonso VI, they conquered Toledo.12 Toledo is situated where the Moorish Al-Andalus and the Christian kingdoms of Castile and Leon border each other, so the conquering of Toledo was a push in the right direction for the Christian kings' ultimate goal of expelling the Moors from Spain. In the northeast, Alfonso I of Aragon began consolidating his power and conquered Zaragoza by 1134, and joined with Barcelona in 1137 to form the Kingdom of Aragon. By this point, the Muslim empire was facing many issues in trying to run their territories and were slowly losing their sphere of power in the south. King Fernando III of Castile was able to penetrate Al-Andalus and conquer the Andalusian cities of Cordoba and Seville in the mid-thirteenth century. So, when the two kingdoms of Aragon and Castile prevailed over their Christian counterparts, they were left with only the Emirate of Granada as their last steppingstone to banish Muslim rule from the peninsula. King Fernando II of Aragon and Queen Isabella of Castile married in 1469 and this consolidated the royal authority of Spain.13 In January of 1492, the city of Granada fell to the Spanish forces and this ended the 780 years of Muslim control in the Iberian Peninsula. This was the final act of La Reconquista and the beginning of the age of Los Reyes Católicos or 'The Catholic Kings.' King Ferdinand and Queen 12 Phillips and Phillips, 306. 13 Phillips and Phillips, 116. 8 Isabela ruled into the first few years of the sixteenth century, which is marked as the beginning of the Spanish Inquisition—a judicial institution that was used to combat heresy in Spain. Islam and Christianity under Christian Rule Islam first began to submit to Christian rule during the period when the Christian kingdoms were all building up their states and conquering each other in the eleventh century. When Toledo was captured in 1085, allowing the Muslims to stay was crucial to the economic stability and the intellectual advancement of Christian society.14 With the expulsion of the Moors came the expulsion of their religion and began the institution of Christianity, more specifically Catholicism. The immediate issue that the church saw after the reconquest of Spanish cities was the need to introduce their ecclesiastical structure, so they began to assign bishops to these major cities in addition to creating two new ecclesiastical provinces.15 This rapid organization and dispersion of the Catholic religion in previously Islamic territories was not good news for those Muslims still living in Spain after the reconquest. The Christians could not simply expel the Muslims because in some places they made up the majority of the population and were an integral part of the economy for the country.16 Muslims who continued to live under Christian ruler adopted the name mudéjares or 'mudejars' in English. This name is derived from the Arabic word mudajan meaning 'permitted to remain' with a colloquial implication of 'tamed or domesticated.'17 Ironically, the same way the minorities were treated under Islamic rule, to include Christians, was now how the Muslims were treated under Christian rule. The Mudejars would practice their religion, law, and customs in addition to being permitted to continue their 14 Watt, A History of Islamic Spain, 150. 15 O'Callaghan, A History of Medieval Spain, 488. 16 Watt, A History of Islamic Spain, 151. 17 Watt, 151. 9 craft so long as they paid a tax. It was not uncommon for these minority groups to distinguish themselves by dressing differently and even inhabiting different quarters of town. During the thirteenth and fourteenth centuries, a period known as the Mudejar age, it is evident that there is a culture common to both Christians and Muslims, and that coexistence, to the point of assimilation, was possible. However, it is important to note that the Christians, being the dominant power, were selective in what they chose to assimilate. The most evident piece demonstrating assimilation is the artistic productions, both architecturally and literarily. It was obvious that incorporating the Muslims into society was necessary and beneficial, but towards the end of the fifteenth century, economic disparages were becoming obvious and the Mudejars were the wealthier of the two groups. This jealousy and animosity led to a growing prejudice of Mudejars and once Ferdinand and Isabella unified the peninsula, they turned this prejudice into policy. The previous flirtation of religious tolerance was coming to an end, but due to the policy written for the surrender of Granada, many people of Islamic faith were briefly safe in 1492, so these religiously intolerant policies attacked other groups, namely the Jewish factions of the country. This period of brutal intolerance is known as the Inquisition, and it drastically influenced Spanish society for the years to follow, to include Miguel de Cervantes's Don Quixote of La Mancha. Part II: Survey of Muslim Architecture in Andalusia Moorish architecture is something that when one sees it, they know it. It is a mixture of oriental and occidental to create a recognizable and unique form of architecture. There are certain staple architectural features that help make this style so well-known and are also the features that other cultures adopt simply because of their beauty. Some of these features include 10 stone parapets with Islamic crenellations, horseshoe windows and doors, towers sometimes evoking a minaret, domes, arches, slender pillars, and many of these features were typically constructed with alternating colors of yellow and red brick and stone.18 The following figures demonstrate these architectural features. 18 Kalmar, "Moorish Style: Orientalism, the Jews, and Synagogue Architecture," 73. Figure 4 (above): The series of arches and horshoe shaped doors. Taken by Alexandra Parent in the Royal Alcazar in Seville, Spain. January 31, 2018. Figure 5 (below): The classic Islamic crennelations and attention to detail that characterizes all of Islamic architecture. This is also exemplatory of the domes that were utilized in Moorish architecture. Taken by Alexandra Parent at the Royal Alcazar in Seville, Spain. January 31, 2018. Figure 3: The slender pillars and open courtyards. Taken by Alexandra Parent at the Alhambra in Granada, Spain. February 23, 2018. Figure 6: The Torre del Oro or Tower of Gold located in Seville, Spain. Exemplifies the use of towers and minarets in Islamic architecture. Taken by Alexandra Parent in Seville, Spain. April 12, 2018. 11 19 These features are apparent throughout all the everyday buildings within the cities of Al- Andalus, but they also came together to make great, exceptional buildings. One in particular is the Great Mosque in Cordoba. This was built when the religion of Islam was only a century old, so it is renowned as one of the first mosques ever built. This mosque is truly grandeur in architectural style in addition to sheer size. In Islamic faith, it is forbidden to depict Allah, or any religious figure, so the traditional methods of using a painting to inspire religious awe was not possible, thus allowing for architecture to take its place. As seen in Figure 7, the rows of archways are seemingly never ending and absolutely uniform. 20 The architectural margin of the mosque (Fig 8 and Fig 10.D), which Cervantes metaphorizes with the annotation of Dulcinea written on the margin in Don Quixote, refers to the most important part of the mosque: the inscriptions. In the Islamic religion, as aforementioned, worshipping any idols or to depict Allah, Muhammad, or any other important religious figures 20 "The Mosque-Cathedral of Cordoba (Spain)." Accessed February 19, 2020. https://www.turismodecordoba.org/the-mosque-cathedral-of-cordoba-spain. Figure 7: The Great Mosque located in Cordoba, Spain. Known for the uniformity and neverending archways and pillars. From Internet: public domain.20 12 through paintings are prohibited. So, the role of the inscriptions becomes the most important and revered part of the mosque much like the depiction of Jesus on the cross is worshipped by Christians. This is because the inscriptions are the holy words of the Koran. The phrase most 21commonly inscribed in these architectural margins are 'only Allah is victorious.' The metaphor Cervantes makes between the architectural and literary margin is developed to a second degree with the handwriting in the margin of the manuscript being Arabic calligraphy. This can be compared to the inscriptions in the architectural margin of the mosques, which are also written in Arabic calligraphy. This type of writing is very distinct from Western modes of writing because the purpose of Arabic calligraphy is "no como un medio utilitario de 21 Fernando Aznar, La Alhambra y el Generalife de Granada. Monumentos, 12. Figure 10: Architecture of the Mosque21 (from left to right and top to bottom): A) ataurique B) interlacing decoration C) calligraphy in the margin of the wall with scripture "Only Allah is Victorious". Also shown in Fig 11. D) horseshoe arc E) muqarnas F) half horseshoe arcs G) arc with muqarnas H) column with crowned capital Figure 8 (above): The horsehoe shaped windows and use of alternating colors and very detailed crennelations. The Arabic calligraphy can be seen above the windows. Taken by Alexandra Parent at the Alhambra in Granada, Spain. February 23, 2018. Figure 9 (above): Fig 8 on a closer scale to better see the calligraphy 13 comunicación entre los hombres sino como un medio sagrado de comunicación entre Dios y los hombres," meaning, it is not like a utilitarian means of communication between humans, but rather a sacred means of communication between God and men.22 This type of calligraphy that Arabs place in the margins of their mosques obviously have religious value and is called caligrafía cúfica or 'Kufic calligraphy' as is shown in Figure 11. 23 The text written in Arabic calligraphy in the margin of the wall of the mosque is epigrafía. It is present in all mosques and throughout the royal palace known as La Alhambra in Granada. As Fernando Aznar explains, "El texto tiene gran importancia en la decoración. Frases que ensalzan a Alá, o que hace referencia a las bellezas del lugar donde se encuentra, ditando a veces a los constructores de cada zona, se reparten por todos los muros de la residencia real."24This quote says that text has great importance in the decoration of the buildings, and that the phrases that praise Allah, or that refers to the beauties of the place where Allah is located, are all throughout the royal palace. It amplifies the important role that language has in religious symbols. 22 "La Caligrafía Árabe." 23 "Arabic Inscription." Alamy. Accessed February 24, 2020. https://www.alamy.com/stock-photo-arabic-inscription- carved-in-a-palace-wall-of-the-alhambra-in-granada-17181753.html. 24 Fernando Aznar, La Alhambra y el Generalife de Granada. Monumentos, 12. Figure 11: An example of Kufic calligraphy. The style of the Arabic writing in this image is classically used in Islamic mosques to state the word of Allah from the Holy Koran. This is the architectural margin. From Internet: public domain.23 14 Moorish Architectural Influence Under Christian Rule As the Christians slowly began organizing themselves into kingdoms and conquering Moorish cities in Al-Andalus, two incredibly different cultures met each other. As previously stated, an assimilation of sorts was taking place by the Christians who were adopting Islamic practices and other elements of their culture. Architecture was one of these elements that Christian rulers not only preserved, but in some cases built from bottom up utilizing these inherently Moorish styles. Using the example of the Mosque of Cordoba, it is important to note that in the middle of this Islamic prayer hall, there is something unknown to Islam; a Catholic Cathedral (Fig. 12, 13, and 14). This addition was made in the sixteenth century after the Moors were abolished from Iberia. The rulers who erected this cathedral demolished the central columns in order to make room for the Christian edifices, however, Charles V recognized the gravity of this action and how it drastically changed the ambiance and historical significance of this architectural feat. This cultural vandalism by the Christians is symbolic of the enforcement and imposition of their religion onto a different group of people. This theme is also apparent in the literary works of the sixteenth and seventeenth centuries to include Don Quixote of La Mancha by Miguel de Cervantes. Figure 12: Located in the middle of the Great Mosque of Cordoba. Christian, gothic architecture meeting with Islamic architectural styles. Taken by Alexandra Parent. January 31, 2018. 15 An example of Mudejar work is the Cathedral of Seville, built after the demolition of a mosque, in order to increase the power of the Christian rulers. The architectural style of the building is very European and gothic with high vaulted ceilings and stained glass.25 As a statement piece for Christianity in former Islamic Spain, it is not expected for one to find traces of Moorish architectural influence, but there is. The Cathedral was built by Christian architects, so there was no lack of qualified Christian craftsmen, however there are qualities inherently Moorish that make its way into this grand architectural achievement. As depicted in Figure 15, the high altar in the Cathedral is adorned in so much detail that it mimics the Moorish tendency to not leave any blank space. The incessant ornamental decoration style that was a part of Islamic Spain bled into and permeated traditional Christian and European styles of architecture making its way into the very soul of Christian craftsmanship. Although the Christian Spanish rulers 25 BBC Worldwide Learning, The Moorish South: Art in Muslim and Christian Spain from 711-1492. Figure 13 (right): Christian altar located in the middle of the Great Mosque of Cordoba in Spain. Taken by Alexandra Parent. January 31, 2018. Figure 14 (left): Example of Christianity inserting itself into Muslim architecture. Taken by Alexandra Parent. January 31, 2018. 16 erected this cathedral as a statement to assert their religious dominance, the Moorish aesthetic had already made its way into the minds of the architects of that era. In addition to this, the minaret attached to the Cathedral of Seville, La Giralda (Figure 16), is evidence of this as well. The construction of this minaret concluded in 1568 and is the twin tower to the city of Marrakech. Having begun construction in 1184, La Giralda is host to the visible mixing of Moorish and Christian culture. Through the stonework, inscriptions, and different styles used, La Giralda is evidence of this assimilation of cultural and architectural practices. 26 Perhaps the most notable architectural feat in regard to Moorish influence on Christianity is seen in the Real Alcázar, or Royal Alcazar. At first glance, it is a very distinct Moorish-looking building in terms of architecture; it contains the classic Moorish archways, courtyards, crenellations and pillars (Fig 17 and 18), so it would be reasonable to conclude that it was 26 "Cathedral of Seville. Aerial View." Accessed February 24, 2020. https://seebybike.com/blog/must-see-cathedral-and- alcazar-of-seville/cathedral-of-seville-aerial-view/. Figure 15 (right): The altar located inside the Cathedral of Seville. Known for it's incredulous detail and extravagant style that is suspected to be a result of lingering Moorish influences. Taken by Alexandra Parent. January 31, 2018. Figure 16 (left): An aerial view of the Cathedral of Seville. It includes many influences of Morrish architecture to include the large tower known as La Giralda, the minarets all over the building, and the many domes that make up the cathedral. From Internet: public domain.26 17 constructed under Islamic rule. However, Christian king Peter of Castile, also known as Peter the Cruel, commissioned the Alcazar as his royal palace in the fourteenth century. He made the Alcazar identical to the architectural stylings of the Spanish Middle Ages. So, the question arises as to why a Christian ruler would deliberately choose Islamic decoration? The answer is that it comes down to power. By appropriating the Islamic art and traditional expressions, the Christian ruler projects a sort of authority over the minority subjects.27 The Moorish expressions of wealth and power are understood differently than traditional Europeans, so by creating something that the Muslim population would recognize as powerful, Peter the Cruel wielded a sort of power over the Mudejars. 27 Fernández, "Second Flowering: Art of the Mudejars." Figure 17 (left): The courtyard of the Royal Alcazar. Despite being built by a Christian king, it has many, if not completely full of, influences from Islamic architecture. Note, the pillars, the archways, the courtyard, the crennelations. Taken by Alexandra Parent. January 31, 2018. Figure 18 (right): The Royal Alcazar in Seville, Spain. This wall has both Christian and Islamic influences. Note the differences between the lower floor and the second floor of the archways. The bottom is much more functional and plainer, like traditional Christian architecture whereas the top portions are much more detailed and colorful such as depicted by Islamic architecture. Taken by Alexandra Parent. January 31, 2018. 18 Part III: The Literary Margin Treated in the Episode of the Lost Manuscript in Volume I: Chapters Eight and Nine of Cervantes's Don Quixote When reading Don Quixote, the reader is frequently taken off the main narrative path involving the adventures of the main characters, the knight and his squire Sancho Panza, and led down secondary narratives involving encounters with characters who interrupt the main narration with tales of their own stories of love, captivity, and triumph. The complexity of the narrative shows the novel to be an amalgam of many different short novels, much like the way of the river Amazon, which is fed by many smaller rivers, at the heart of which is Cervantes's parody of books of chivalry. Nevertheless, the one unchanging constant is the way the novel opens a window onto the life and times of the man who wrote it. Cervantes's novel reflects his lived experience rooted in multicultural society whose heterogeneity was the source of Spain's economic and agricultural well-being. Cervantes saw the well-being of his country destroyed by the Hapsburg dynasty's religious intolerance and persecution of minorities who did not convert from their Jewish or Muslim faith. Cervantes himself was of Jewish ancestry. His father was a surgeon, a vocation known to be practiced by Jews. Cryptic references to his Jewish ancestry appear in the portada, or cover page of this novel. For example, the phrase from the book of Job—after darkness light is hoped for—and references to their inability to worship on the Sabbath appear in the first chapter of the novel; a day when the Jewish population must be in duelos and quebrantos, or 'pain and suffering'. While a student, Cervantes was arrested and ordered to have his right hand cut off for allegedly shooting a man who had insulted his sisters. Cervantes escaped punishment by fleeing to Italy from where he joined the Holy League (an alliance among the Vatican, France, and Spain) in the Battle of Lepanto, a major battle against the Turks in the waters of the 19 Mediterranean, during which Cervantes lost the use of his left hand. After his distinguished military service in this major victory against the Turks, Cervantes was taken captive and held prisoner for five years in Algeria. His profound understanding of the Islamic world of the Maghreb, as the northern region of Africa is known, is reflected throughout Don Quixote. Upon return to Spain, he obtained work as a tax collector tasked with gathering funds throughout Andalusia for the construction of the Spanish Armada. His detailed knowledge of the geography and customs of Southern Spain is reflected throughout the novel as well. Cervantes's experiences from his military expedition against the Turks, his years in captivity in northern Africa, his travels through Andalusia, and his Jewish ancestry can be added as another factor that forged the broad multicultural perspectivism formed in his novel. As a student, Cervantes was taught by Lope de Hoyos, a known follower of the Dutch humanist philosopher Erasmus of Rotterdam. Erasmus criticized the empty ritual of the Catholic Church as well as its intolerance for Christians, especially followers of Martin Luther, who sought an unmediated religious relationship with God; one that did not require mediation by a Catholic priest. The teachings of Erasmus, an intellect who denounced the hypocrisy of the Catholic Church and its persecution of minorities and different versions of Christianity, are embraced by Cervantes and find expression in a covert manner in Don Quixote (II: 22-23).28 The episode of the lost manuscript (Volume I:8-9) reflects the perspective of multiculturalism and diversity Cervantes gained from the life experiences outlined above. Chapter eight is first and foremost about Don Quixotes's iconic battle with the windmills, the most well-known episode of the novel. Don Quixote's illusion leads him to believe that the windmills were originally giants that have been transformed into windmills by his enemy, the 28 Judith Stallings-Ward, "Tiny (Erasmian) Dagger or Large Poniard? Metonymy vs. Metaphor in the Cave of Montesinos Episode in Don Quixote." 20 wizard Freston, to cheat Don Quixote from a victory in battle against them. The deception of the knight conveys Cervantes's use of humorous parody to denounce the books of chivalry whose fantasy version of reality has brainwashed Don Quixote. A subsequent adventure in this chapter reveals Don Quixote has another lapse of reason. He believes that a Basque woman travelling to Seville, preceded by two Benedictine friars who are not in her party, and surrounded by her own men on horseback, is a princess being kidnapped. Upon observing once again his master's mind in the grip of delusion, Don Quixote's squire Sancho Panza replies, "This will be worse than the windmills."29 This foreshadows the battle that Don Quixote will ultimately have with the Basque. At the end of Chapter eight, we are left with both men having their swords unsheathed and raised at each other, but then the narration of the story abruptly stops. The narrator, a literary form of Cervantes inserted into the story by the real historical Cervantes, begins to speak directly to the reader as if in an informal conversation with them to convey that the end of the scene and the rest of the history are missing.30 This narrative style continues into Part II, chapter nine when the narrator begins a search for the missing manuscript. In this chapter we are brought to Toledo and the narrator brings the reader through the Alcaná market. The narrator Cervantes tells the story of his journey to find the manuscript in the market and how he comes across a young boy trying to sell him some notebooks, old torn papers, and other small commodities. Cervantes is inclined to pick up a certain book that the boy has and realizes the script on the front is in Arabic. Since he could not read Arabic, he finds a Morisco aljamiado, so called for their ability to speak both Arabic and Spanish, who can help translate the manuscript. It was not difficult to find this person and soon Cervantes flipped to the middle of the book and asked the Morisco to translate. Cervantes points out the availability of translators of 29 Cervantes, Don Quixote, 62. 30 Cervantes, 65. 21 all classic languages in the market, thus underscoring the advantage of multicultural spaces such as the markets of Spain. As the translator--the Morisco aljamiado--began to read the page, he laughed at something written in the margin: it stated, "'This Dulcinea of Toboso, referred to so often in this history, they say had the best hand for salting pork of any woman in La Mancha.'"31 The narrator immediately knew that this was the missing manuscript he was looking for, so he had the Morisco read even more. It is then that the reader learns the novel was originally written in Arabic by the Arab historian Cide Hamete Benengeli. Narrator Cervantes commissions the Morisco to translate the entire novel, paying him in "two arrobas of raisins, and two fanegas of wheat," so that the story of Don Quixote and Sancho Panza can be continued.32 This process of translation of the original manuscript from Arabic to Spanish is now the source of the narrator Cervantes's history of Don Quixote, and it is a collaboration between the literary Christian "Cervantes" and the original Arabic author Cide Hamete Benengeli, delivered through the translator. The reader is now being told the story through someone else's eyes and mind. The novel descends into a rabbit hole of authorship in which, ironically, the new lens is a Morisco translator. This metaphor demonstrates that true Spanish history is written as a compilation between Christianity and Islam, not one or the other, thus demonstrating historical Cervantes's disdain and disapproval of the expulsion of the Moors. Rather, Cervantes displays the importance and necessity of diversity and multiculturalism. The true author, historical Cervantes, also establishes a metaphor between the literary margin, in which the literary Cervantes discovered the novel was indeed Don Quixote, and the architectural margins of the mosque. Cervantes does this in a very clever and implicit manner, 31 Cervantes, 67. 32 Cervantes, 68. 22 otherwise he would be severely censored. Through this implied metaphor of architectural and literary margins, Cervantes is able to write a novel that has commentary to covertly express his condemnation of the Moors and announce his glorification of multiculturalism. The focus of attention placed on the margin of the manuscript wherein Arabic commentary is written calls to mind the architectural margin of the mezquita, or 'mosque', in which the Arabic calligraphy is written. The comparison between the textual margin of Cervantes's manuscript and architectural margin of the walls of the mosque would be easy for the readers of Cervantes's day to recognize given the prevalence of Muslim architecture throughout Spain, as my survey in the first part of this essay shows. Furthermore, the handwriting in Arabic by the Arab historian easily calls to mind the calligraphy used for citations from the Koran. The Arabic commentary—associated with the authoritative word of the Koran placed in the margin of the walls of the mosque—second guesses the religious purity of Dulcinea, the object of courtly worship by the Christian knight. When the translator points out the Arab historian's commentary in the margin of the manuscript, that 'the Lady Dulcinea has the best hand at salting pork,' he taints her purity by placing her in contact with a food source that is considered polluted for Muslims. The comment casts Dulcinea in tainted light. The Arab historian's questioning of religious purity occurs in tandem with the questioning of the authority or authorship of the history of Don Quixote. The literary Cervantes is a Christian writer, but he is not the true author of the original manuscript; the Arab historian Cide Hamete claims true authorship; and Dulcinea is not the pillar of religious purity she is perceived to be. The play with the double meaning of the margin (textual vs architectural) occurs with the play of spatial perspective between margin vs center. The reader sees through Cervantes's use of the metaphor as a multicultural perspective that questions the absolute status of Christian 23 authority and Christian purity. The play with meaning and perspective in Cervantes's treatment of the margin in chapters eight and nine may be taken to one final and third level of development. The margin, shown to be central in connection with the ruptured or severed manuscript, is a covert expression for Cervantes's esteem for the contributions to Spanish society by the Muslim population of his country and his condemnation for their expulsion by governmental degree from Spain. In the eyes of Cervantes, this broke of the backbone of Spain's culture and economy since the Arab population made up an incredibly large portion of the Iberian Peninsula. Cervantes accomplishes this by, not only changing chapters, but beginning a whole new section of the novel. Part I concludes with chapter eight and the pending battle between Don Quixote and the Basque, then Part II begins with the narrator Cervantes informing the reader of his journey to find the rest of the novel. Being wary of the censorship that plagued others during the Inquisition, Cervantes chose this metaphorical approach to convey his true sentiments about the situation of Spain at this moment in history. This rupture in Don Quixote's history is reflective of the moment in Spain's history where law has been decreed to banish something so inherent to the nation itself: the Moorish people. By placing these episodes side by side, Cervantes invites the reader to compare the delusion of the Hapsburg imperial vision and its expulsion of the Moors with the episode of the windmills. The blindness of Spain's government seems even more laughable than Don Quixote's own misguided attack on the windmills. Cervantes's play with the margin allows him to express his views on multiculturalism in an indirect manner that allowed him to escape censorship by the Inquisition. The Inquisition was not savvy enough to realize that this profound division between Part I and II is symbolic of the division of tolerant Spain into an intolerant Spain. After Cervantes 24 died, the Inquisition did censor and expurgate a passage that was considered too directly stated. In chapter thirteen, Don Quixote is once again declaring his servitude and attesting to the beauty of his beloved Dulcinea of Toboso. In his description to Vivaldo, he uses a Petrarchan metaphor, a very classical and renaissance style of poetry, to describe Dulcinea. Don Quixote states (Volume I:13): "Her tresses are gold, her forehead Elysian fields, her eyebrows the arches of heaven, her eyes suns, her cheeks roses, her lips coral, her teeth pearls, her necklace alabaster, her bosom marble, her hands ivory, her skin white as snow, and the parts that modesty hides from human eyes are such, or so I believed and understand, that the most discerning consideration can only praise them but not compare them."33 While eloquently put, Cervantes is nonetheless making references to the private areas of Dulcinea's body and thus was censored by the Catholic Church in 1624 after his death; they dared not censor him before since his novel made him so beloved by the people. Cervantes was too clever to have to follow the rules. His questioning of authority was apparent from the very opening words of the novel when he writes, "[s]omewhere in La Mancha, in a place whose name I do not care to remember…"34 Cervantes conveys how exact places and names are all arbitrary and are not relevant to the novel. This echoes Cervantes own questioning of authority and Spain's religious Inquisition going on that persecuted the Moors and other minorities alike. 33 Cervantes, Don Quixote, 91. 34 Cervantes, 19. 25 Conclusion The religious tolerance and interdependence between minorities of Al-Andalus, which are reflected through the architecture of Andalusia and also underscored in Cervantes's Don Quixote through the metaphorical treatment of the literary margin in the episode of the lost manuscript, seems evermore elusive today. In light of the divisiveness and racism rampant in our society that mars efforts toward multiculturalism and diversity, such as those undertaken at universities like Norwich, tolerance seems like the impossible dream that is the object of the quest of the chivalrous knight Don Quixote. 26 Bibliography Arnold, Thomas Walker. The Preaching of Islam; A History of the Propagation of the Muslim Faith. New York: C. Scribner's sons, 1913. http://archive.org/details/preachingofisla00arno. Aznar, Fernando. La Alhambra y el Generalife de Granada. Monumentos Declared of World Interest by Unescco. Mariarsa:1985. BBC Worldwide Learning. The Moorish South: Art in Muslim and Christian Spain from 711- 1492. Documentary Film. The Art of Spain: From the Moors to Modernism, 2009. https://fod.infobase.com/p_ViewVideo.aspx?xtid=39408. Cervantes, Miguel. Don Quixote. Translated by Edith Grossman. 5 edition. New York: Harper Collins, 2003. Fernández, Luis. La Historia de España en 100 preguntas. Madrid, Spain: Ediciones Nowtilus, 2019. https://ebookcentral.proquest.com/lib/norwich/reader.action?docID=5703133&ppg=1. Fernández, María Luisa. "Second Flowering: Art of the Mudejars." Saudi Aramco World, The Legacy of Al-Andalus, 44, no. 1 (February 1993): 36–41. Harsolia, Khadija Mohiuddin. "Captivity, Confinement and Resistance in Mudejar and Morisco Literature." University of California, Riverside, 2016. WorldCat.org. https://search.proquest.com/docview/1849025713?accountid=14521. Kalmar, Ivan Davidson. "Moorish Style: Orientalism, the Jews, and Synagogue Architecture." Jewish Social Studies 7, no. 3 (2001): 68–100. "La Caligrafía Árabe." Accessed February 21, 2020. http://www.arabespanol.org/cultura/caligrafia.htm. Maíz Chacón, Jorge. Breve historia de los reinos ibéricos. 1a. edición. Quintaesencia ; 6. Barcelona: Ariel, 2013. http://catdir.loc.gov/catdir/enhancements/fy1313/2013369841- b.html. Menocal, Maria Rosa. The Ornament of the World: How Muslims, Jews and Christians Created a Culture of Tolerance in Medieval Spain. Reprint edition. Boston: Back Bay Books, 2003. O'Callaghan, Joseph. A History of Medieval Spain. 1st ed. Ithaca, New York: Cornell University Press, 1975. https://ebookcentral.proquest.com/lib/norwich/detail.action?docID=3138541. 27 Phillips, William D., and Carla Rahn Phillips. A Concise History of Spain. Cambridge Concise Histories. Cambridge: Cambridge University Press, 2010. https://library.norwich.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true &db=e000xna&AN=490553&scope=site. Raquejo, Tonia. "The 'Arab Cathedrals': Moorish Architecture as Seen by British Travellers." The Burlington Magazine 128, no. 1001 (1986): 555–63. Sheren, Ila Nicole. "Transcultured Architecture: Mudéjar's Epic Journey Reinterpreted." Contemporaneity: Historical Presence in Visual Culture 1 (June 1, 2011): 137–51. https://doi.org/10.5195/contemp.2011.5. Stallings-Ward, Judith. "Tiny (Erasmian) Dagger or Large Poniard? Metonymy vs. Metaphor in the Cave of Montesinos Episode in Don Quixote." Comparative Literature Studies. 43.4 (2006) special issue: Don Quixote and 400 Years of World Literature. 441-65. Stallings-Ward, Judith. Gerardo Diego´s Creation Myth of Music: Fábula de Equis y Zeda. London: Routledge, 2020. Urquízar-Herrera, Antonio. Admiration and Awe: Morisco Buildings and Identity Negotiations in Early Modern Spanish Historiography. 1 online resource (289 pages) vols. Oxford: OUP Oxford, 2017. http://public.ebookcentral.proquest.com/choice/publicfullrecord.aspx?p=4850548. Watt, W. Montgomery. A History of Islamic Spain. Islamic Surveys; 4. Edinburgh: Edinburgh University Press, 1977.