Suchergebnisse

Publisher's version (útgefin grein) ; The etiology of monoclonal gammopathy of undetermined significance (MGUS), the precursor state of multiple myeloma (MM), is mostly unknown and no studies have been conducted on the effect of diet on MGUS or progression from MGUS to MM. We aimed to explore the association between common foods and MGUS and progression to MM. Data from the population-based AGES Study (N = 5,764) were utilized. Food frequency questionnaire was used to assess dietary intake during adolescence, midlife, and late life. Serum protein electrophoresis and serum free light-chain assay was performed to identify MGUS (n = 300) and LC-MGUS cases (n = 275). We cross linked our data with the Icelandic Cancer Registry to find cases of MM in the study group. We found that intake of fruit at least three times per week during adolescence was associated with lower risk of MGUS when compared to lower fruit consumption (OR = 0.62, 95% CI 0.41–0.95). We additionally found that intake of fruit at least three times per week during the late life period was associated with decreased risk of progressing from MGUS to MM (HR = 0.34, 95% CI 0.13–0.89) when compared to lower intake. Adolescent intake of fruit may reduce risk of MGUS, whereas fruit intake after MGUS onset may reduce risk of progressing to MM. Our findings suggest that diet might alter the risk of developing MGUS and progression to MM. ; The AGES-Reykjavik Study was funded by NIH contract N01-AG-012100, the Intramural Research Program of the National Institute on Aging, by the Icelandic Heart Association, and the Icelandic Parliament. This work was supported by the Icelandic Centre for Research, RANNIS (S.Y. Kristinsson), the Landspitali University Hospital Research Fund (S.Y. Kristinsson), the Karolinska Instituted Foundations (S.Y. Kristinsson), the Marie Curie CIG (S.Y. Kristinsson), and the Memorial Sloan Kettering Core Grant (P30 CA008748) from the National Cancer Institute (O.Landgren). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Peer Reviewed

Multiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n=15) are characterized by later initiation in the patient's life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable. The factors that are associated with myeloma precursor condition progression are not well understood. Here the authors find that monoclonal gammopathies of undetermined significance and smoldering myelomas that did not progress to multiple myelomas have a distinct genomic profile and emerge later in the patient's life. ; We want to thank Dr. Vincent S Rajkumar for important and useful scientific feedback on the final draft. This work was supported by the Society of Memorial Sloan Kettering, by the Sylvester Comprehensive Cancer Center NCI Core Grant (P30 CA 240139), by the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748), by the Multiple Myeloma Research Foundation (MMRF), by the Perelman Family Foundation, and by the Riney Family Multiple Myeloma Research Program Fund. F.M. is supported by the American Society of Hematology, the International Myeloma Foundation and The Society of Memorial Sloan Kettering Cancer Center. N.B. is funded by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement no. 817997). K.H.M. is supported by the Royal Australasian College of Physicians Dr. Helen Rarity McCreanor Traveling Fellowship. This study is part of the Limburg Clinical Research Center (LCRC) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Additionally, this research is supported by Limburgs Kankerfonds, and LiveALife. ; Maura, F (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA. Landgren, O; Maura, F (corresponding author), Univ Miami, Sylvester Comprehens Canc Ctr, Myeloma Program, Miami, FL 33124 USA. col15@miami.edu; fxm557@med.miami.edu

Funding Information: P.K. is an employee of The Binding Site. BGMD has done consultancy for Amgen, Janssen, Celgene, Takeda. S.H. is the director of The Binding Site. O.L. has received research funding from: National Institutes of Health (NIH), National Cancer Institute (NCI), U.S. Food and Drug Administration (FDA), Multiple Myeloma Research Foundation (MMRF), International Myeloma Foundation (IMF), Leukemia and Lymphoma Society (LLS), Perelman Family Foundation, Rising Tide Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; Honoraria/ad boards: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and serves on Independent Data Monitoring Committees (IDMCs) for clinical trials lead by Takeda, Merck, Janssen, Theradex. S.Y.K. has received research funding from International Myeloma Foundation, European Research Council, Icelandic Center for Research (Rannís), Amgen, Celgene. The remaining authors declare no competing interests. Funding Information: The iStopMM study is funded by the Black Swan Research Initiative by the International Myeloma Foundation and the Icelandic Centre for Research (grant agreement No 173857). Furthermore, this project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 716677). Screening tests are performed by The Binding Site Ltd. Birmingham, UK. Additional funding is provided by the University of Iceland, Landspítali University Hospital, and the Icelandic Cancer Society. Crosslinking of study data to national registries is performed by the Icelandic Directorate of Health and the Icelandic Cancer Society. The study is made possible by the hundreds of nurses, laboratory technicians, and physicians around Iceland who collect blood samples from participants for screening or during follow-up and provide clinical care that is not part of the study. Icelandic and International myeloma patient organizations including ...