Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 35, Issue 20, Pages 2240-+Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2016.69.4935
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Funding
- Association for Cancer Research [AIRC] [IG16933]
- Ministere de l'E'conomie, Innovation et Exportation du Quebec Grant [PSR-SIIRI-701]
- Government of Canada through Genome Canada
- Canadian Institutes of Health Research [GPH-129344, CRN-87521]
- Ministere de l'E'conomie, de la Science et de l'Innovation du Quebec through Genome Quebec
- Quebec Breast Cancer Foundation
- US National Institutes of Health (NIH) [1U19-CA148065, X01-HG007492, C1287/A10118, C1287/A11990]
- Cancer Research UK [C1287/A16563, C12292/A20861, C12292/A11174, C5047/A8385]
- Odense University Hospital Research Foundation (Denmark)
- National R&D Program for Cancer Control, Ministry of Health and Welfare (Republic of Korea) [1420190]
- Breast Cancer Research Foundation
- National Health and Medical Research Council (Australia)
- German Cancer Aid [110837]
- Fondation ARC [SAE20131200623]
- Canadian Institutes of Health Research
- Ministere de l'Economie, de la Science et de l'Innovation du Quebec through Genome Quebec
- Ministere de l'Economie, Innovation et Exportation du Quebec Grant [PSR-SIIRI-701]
- National Cancer Institute [UM1-CA164920, RC4CA153828, CA125183, R01-CA142996, 1U01-CA161032]
- Lithuania Research Council of Lithuania [SEN-18/2015]
- Morris and Horowitz Families Professorship
- Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI08/1120]
- Mutua Madrilena Foundation (FMMA)
- Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2014-57680-R]
- Office of the Director, NIH
- Italian Association of Cancer Research [IG16933, IG12821, IG15547]
- Fondazione IRCCS Istituto Nazionale Tumori
- Sapienza University of Rome
- ITT (Istituto Toscano Tumori)
- European Union
- National Strategic Reference Framework Research Funding Program of the General Secretariat for Research and Technology [SYN11_10_19 NBCA]
- DKFZ
- NIH Research (NIHR)
- NIHR
- Royal Marsden NHS Foundation Trust
- University of Kansas Cancer Center [P30-CA168524]
- Kansas Bioscience Authority Eminent Scholar Program
- Chancellors Distinguished Chair in Biomedical Sciences Professorship
- Ligue Nationale Contre le Cancer
- Association Le cancer du sein, parlons-en! Award
- French National Institute of Cancer
- IWT
- ISCIII (Spain) [RD12/00369/0006, 15/00059]
- European Regional Development FEDER funds
- Helsinki University Hospital Research Fund
- Academy of Finland [266528]
- Finnish Cancer Society
- Sigrid Juselius Foundation
- Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]
- Netherlands Organization of Scientific Research [NWO 91109024]
- Pink Ribbon Grants [110005, 2014-187.WO76]
- BBMRI [NWO 184.021.007/CP46]
- Transcan grant [12-054]
- Hungarian Research Grants [KTIA-OTKA CK-80745, OTKA K-112228]
- Spanish Instituto de Salud Carlos III funding, an initiative of the Spanish Ministry of Economy and Innovation - European Regional Development FEDER Funds [FIS PI12/02585, FIS PI13/01711]
- Miguel Servet contract (ISCiii)
- Asociacion Espanola Contra el Cancer
- Spanish Health Research Fund
- Carlos III Health Institute
- Catalan Health Institute and Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, PIE13/00022, 2009SGR290, 2014SGR364]
- Icelandic Association
- Landspitali University Hospital Research Fund
- Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]
- Ministero della Salute
- Istituto Oncologico Veneto grant
- Liga Portuguesa Contra o Cancro
- National Breast Cancer Foundation
- Queensland Cancer Fund
- Cancer Council of New South Wales
- Cancer Council of New South, Victoria
- Cancer Council of New South, Tasmania
- Cancer Council of New South, South Australia
- Cancer Foundation of Western Australia
- NHMRC
- Cancer Australia
- US NIH
- NHMRC senior research Fellowship [APP1061779]
- Cancer Council Queensland [APP1086286]
- National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [1020350]
- NIH [CA116167, CA128978, CA176785]
- National Cancer Institute Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- Jewish General Hospital Weekend
- Robert and Kate Niehaus Clinical Cancer Genetics Initiative
- Andrew Sabin Research Fund
- US National Cancer Institute
- Ohio State University Comprehensive Cancer Center
- Ministry of Science, Technology and Innovation, Ministry of Higher Education [UM.C/HlR/MOHE/06]
- Cancer Research Initiatives Foundation
- Malaysian Ministry of Science, Technology, and Innovation, Ministry of Higher Education [UM.C/HIR/MOHE/06]
- Swedish Cancer Society
- Ralph and Marion Falk Medical Research Trust
- Entertainment Industry Fund National Women's Cancer Research Alliance
- Susan G. Komen Foundation
- Frieda G. and Saul F. Shapira BRCA-Associated Cancer Research Program
- Victorian Cancer Agency
- [SAF2010-20493]
- [5U01-CA113916]
- [R01-CA140323]
- [NO2-CP-11019-50]
- [N02-CP-65504]
- Cancer Research UK [17523, 10118, 16563, 15007, 17528, 11174, 12677, 23382] Funding Source: researchfish
- National Breast Cancer Foundation [IF-12-06] Funding Source: researchfish
- National Institute for Health Research [RP-PG-0707-10031, NF-SI-0513-10076, NF-SI-0510-10096] Funding Source: researchfish
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PurposeBRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigatedfor the first time to our knowledgeassociations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction.Materials and MethodsWe genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights.ResultsIn male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 x 10(-6)). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 x 10(-9)). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively.ConclusionPRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.
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