Journal article

Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Paolo Peterlongo, Jenny Chang-Claude, Kirsten B Moysich, Anja Rudolph, Rita K Schmutzler, Jacques Simard, Penny Soucy, Rosalind A Eeles, Douglas F Easton, Ute Hamann, Stefan Wilkening, Bowang Chen, Matti A Rookus, MarjankaK Schmidt, Frederieke H van der Baan, Amanda B Spurdle, Logan C Walker, Felicity Lose, Ana-Teresa Maia, Marco Montagna Show all

Cancer Epidemiology Biomarkers & Prevention | AMER ASSOC CANCER RESEARCH | Published : 2015

Abstract

BACKGROUND: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. METHODS: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. RE..

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University of Melbourne Researchers

Grants

Awarded by European Community (COGS)


Awarded by Cancer Research UK


Awarded by NIH


Awarded by Post-Cancer GWAS initiative


Awarded by Department of Defence


Awarded by National Cancer Institute


Awarded by Research Council of Lithuania


Awarded by Spanish Association against Cancer


Awarded by German Cancer Aid


Awarded by Helsinki University Central Hospital Research Fund, Academy of Finland


Awarded by Dutch Cancer Society


Awarded by Netherlands Organization of Scientific Research


Awarded by Pink Ribbon


Awarded by BBMRI


Awarded by Hungarian Research Grants


Awarded by Catalan Health Institute and Autonomous Government of Catalonia


Awarded by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer


Awarded by U.S. Department of Defence Ovarian Cancer Idea award


Awarded by Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute - American Cancer Society Early Detection Professorship


Awarded by University of Kansas Cancer Center


Awarded by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank


Awarded by GOG Statistical and Data Center


Awarded by NCI's Community Clinical Oncology Program (CCOP) grant


Awarded by Canadian Breast Cancer Research Alliance-grant


Awarded by Ministry of Economic Development, Innovation and Export Trade - grant


Awarded by ISCIII



Awarded by National Institute for Health Research


Awarded by National Breast Cancer Foundation


Awarded by The Francis Crick Institute


Awarded by DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL CENTER FOR RESEARCH RESOURCES


Funding Acknowledgements

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/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/ A15007, C5047/A10692), the NIH (CA128978) and Post-Cancer GWAS initiative (1U19CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAMEON 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, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. BFBOCC was partly supported by: Research Council of Lithuania grant LIG-07/2012; BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg; the CNIO study was supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060 and FISPI12/00070 and Mutua Madrilena Foundation (FMMA); City of Hope Clinical Cancer Genetics Community Research Network and the Hereditary Cancer Research Registry (COH-CCGCRN) was supported in part by Award Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, NIH. CONSIT TEAM was partially supported by funds from Italian citizens who allocated the 5 x 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale dei Tumori, according to Italian laws (INT-Institutional strategic projects '5 x 1000'); the DKFZ study was supported by the DKFZ; EMBRACE was supported by Cancer Research UK Grants C1287/A10118, C1287/A16563 and C1287/A17523. 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 were 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 were supported by Cancer Research UK Grant C5047/A8385; the German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is kindly supported by the German Cancer Aid to Rita K. Schmutzler (grant no. 109078) and by the Center for Molecular Medicine Cologne (CMMC); the GEMO study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; 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 HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46; Hungarian Breast and Ovarian Cancer Study (HUNBOCS) was supported by Hungarian Research Grants KTIA OTKA CK-80745 and OTKA K-112228; ICO was sponsored by Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia, contract grant numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, and 2009SGR290; The IHCC was supported by Grant PBZ_KBN_122/P05/2004; The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund; IOVHBOCS was supported by Ministero della Salute and "5 x 1000" Istituto Oncologico Veneto grant; kConFab was supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia; MAYO was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and a grant from the Breast Cancer Research Foundation, the David and Margaret T. Grohne Family Foundation, and the Ting Tsung and Wei Fong Chao Foundation; MSKCC was supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative; OSUCCG was supported by the Ohio State University Comprehensive Cancer Center; SWE-BRCA collaborators are supported by the Swedish Cancer Society; the Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute was funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN).This work was supported by the NEYE Foundation; 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: ARISTEIA, Investing in knowledge society through the European Social Fund; by the University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program; by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and by NCI's Community Clinical Oncology Program (CCOP) grant (CA 101165); by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade - grant #PSR-SIIRI-701; through a grant by the Israel Cancer Association and the funding for the Israeli Inherited Breast Cancer Consortium; by NIH (R01-CA102776 and R01CA083855; by Breast Cancer Research Foundation; by Susan G. Komen Foundation; by Basser Research Center; by RD12/00369/0006 from ISCIII and the European Regional Development funds, Spain and by 1R01 CA149429-01 grant.Susan L. Neuhausen was partially supported by the Morris and Horowitz Families Endowed Professorship; Andrew K. Godwin was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship; the research of Mark H Greene and Phuong L Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019- 50 and N02-CP-65504 with Westat, Inc, Rockville, MD.