Association of Genomic Domains in and with Prostate Cancer Risk and Aggressiveness.

To access publisher's full text version of this article click on the hyperlink belowPathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.National Health and Medical Research Council of Australia National Breast Cancer Foundation Cancer Australia United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) Cancer Research UK European Community (EC) United States Department of Health & Human Services National Institutes of Health (NIH) - USA Post-Cancer GWAS initiative - the GAME-ON initiative United States Department of Defense Canadian Institutes of Health Research (CIHR) Ministry of Economic Development, Innovation and Export Trade Susan G. Komen Breast Cancer Foundation Breast Cancer Research Foundation Ovarian Cancer Research Fund Genome Canada Canadian Institutes of Health Research (CIHR) Ministry of Economy, Science and Innovation through Genome Quebec Quebec Breast Cancer Foundation Research Council of Lithuania Cancer Association of South Africa Spanish Ministry of Health - FEDER funds Spanish Ministry of Economy and Competitiveness (MINECO) Spanish Research Network on Rare diseases (CIBERER) NCI of the NIH United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) United States Department of Health & Human Services National Institutes of Health (NIH) - USA Associazione Italiana per la Ricerca sul Cancro (AIRC) Associazione Italiana per la Ricerca sul Cancro (AIRC) European Union (EU) European Social Fund (ESF) 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 German Cancer Research Center National Institute for Health Research (NIHR) University of Kansas Cancer Center Kansas Bioscience Authority Eminent Scholar Program Chancellors Distinguished Chair in Biomedical Sciences Professorship Mutua Madrilena Foundation (FMMA) Deutsche Krebshilfe European Union (EU) Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases) Ligue nationale contre le cancer Association " Le cancer du sein, parlons-en!" Award Institut National du Cancer (INCA) France United States Department of Health & Human Services National Institutes of Health (NIH) - USA Fisher Center for Hereditary Cancer and Clinical Genomics Research Swing Fore the Cure Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) Instituto de Salud Carlos III Spanish Government CIBERONC from ISCIII (Spain) European Union (EU) Helsinki University Hospital Research Fund Academy of Finland Finnish Cancer Society Sigrid Juselius Foundation KWF Kankerbestrijding Netherlands Organization of Scientific Research grant Pink Ribbon grants BBMRI grant Transcan grant JTC 2012 Cancer Hungarian Research Grants Asociacion Espanola Contra el Cancer (AECC) Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economia y Competitividad) European Union (EU) Institut Catala de la Salut Generalitat de Catalunya Icelandic Association "Walking for Breast Cancer Research" Landspitali University Hospital Research Fund Canadian Institutes of Health Research (CIHR) Ministry of Economic Development, Innovation and Export Trade grant Ministero della Salute and "5 x 100000 Istituto Oncologico Veneto grant United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) Cancer Center Support Grant/Core Grant NCI: the Intramural Research Program of the NCI, NIH Westat, Inc, Rockville, MD Russian Foundation for Basic Research (RFBR) NRG Oncology NRG SDMC grant NRG Administrative Office NRG Tissue Bank NRG Statistical and Data Center Associazione Italiana per la Ricerca sul Cancro (AIRC) Tuscany Institute for Tumors (ITT) grant Ministry of Science, Technology and Innovation, Ministry of Higher Education Ralph and Marion Falk Medical Research Trust Entertainment Industry Fund National Women's Cancer Research Alliance American Cancer Society United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Advancing Translational Sciences (NCATS) Miguel Servet Progam