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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\u2032 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\u20132.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63\u20135.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71\u20134.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12\u201311.54; P = 0.0002). No genotype\u2013phenotype 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Significance:<\/jats:title>\n                  <jats:p>Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1158\/0008-5472.can-19-1840","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T19:45:13Z","timestamp":1573674313000},"page":"624-638","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Association of Genomic Domains in <i>BRCA1<\/i> and <i>BRCA2<\/i> with Prostate Cancer Risk and Aggressiveness"],"prefix":"10.1158","volume":"80","author":[{"given":"Vivek L.","family":"Patel","sequence":"first","affiliation":[{"name":"1Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts."}]},{"given":"Evan L.","family":"Busch","sequence":"additional","affiliation":[{"name":"2Harvard T.H. Chan School of Public Health, Boston, Massachusetts."},{"name":"3Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Tara M.","family":"Friebel","sequence":"additional","affiliation":[{"name":"2Harvard T.H. Chan School of Public Health, Boston, Massachusetts."},{"name":"4Dana-Farber Cancer Institute. Boston, Massachusetts."}]},{"given":"Angel","family":"Cronin","sequence":"additional","affiliation":[{"name":"4Dana-Farber Cancer Institute. Boston, Massachusetts."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-6222","authenticated-orcid":false,"given":"Goska","family":"Leslie","sequence":"additional","affiliation":[{"name":"5Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom."}]},{"given":"Lesley","family":"McGuffog","sequence":"additional","affiliation":[{"name":"5Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1693-0435","authenticated-orcid":false,"given":"Julian","family":"Adlard","sequence":"additional","affiliation":[{"name":"6Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, United Kingdom."}]},{"given":"Simona","family":"Agata","sequence":"additional","affiliation":[{"name":"7Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy."}]},{"given":"Bjarni A.","family":"Agnarsson","sequence":"additional","affiliation":[{"name":"8Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland."},{"name":"9School of Medicine, University of Iceland, Reykjavik, Iceland."}]},{"given":"Munaza","family":"Ahmed","sequence":"additional","affiliation":[{"name":"10North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom."}]},{"given":"Kristiina","family":"Aittom\u00e4ki","sequence":"additional","affiliation":[{"name":"11Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland."}]},{"given":"Elisa","family":"Alducci","sequence":"additional","affiliation":[{"name":"7Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy."}]},{"given":"Irene L.","family":"Andrulis","sequence":"additional","affiliation":[{"name":"12Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada."},{"name":"13Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada."}]},{"given":"Adalgeir","family":"Arason","sequence":"additional","affiliation":[{"name":"8Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland."},{"name":"14BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4523-8808","authenticated-orcid":false,"given":"Norbert","family":"Arnold","sequence":"additional","affiliation":[{"name":"15Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany."}]},{"given":"Grazia","family":"Artioli","sequence":"additional","affiliation":[{"name":"16ULSS 3 Serenissima, U.O.C. Oncologia ed Ematologia Oncologica, Mirano, Venice, Italy."}]},{"given":"Brita","family":"Arver","sequence":"additional","affiliation":[{"name":"17Department of Oncology, Karolinska Institutet, Stockholm, Sweden."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1880-291X","authenticated-orcid":false,"given":"Bernd","family":"Auber","sequence":"additional","affiliation":[{"name":"18Institute of Human Genetics, Hannover Medical School, Hannover, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9364-9778","authenticated-orcid":false,"given":"Jacopo","family":"Azzollini","sequence":"additional","affiliation":[{"name":"19Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale dei Tumori di Milano, Milan, Italy."}]},{"given":"Judith","family":"Balma\u00f1a","sequence":"additional","affiliation":[{"name":"20High Risk and Cancer Prevention Group, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, Barcelona, Spain."}]},{"given":"Rosa B.","family":"Barkardottir","sequence":"additional","affiliation":[{"name":"8Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland."},{"name":"14BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3781-7570","authenticated-orcid":false,"given":"Daniel R.","family":"Barnes","sequence":"additional","affiliation":[{"name":"5Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom."}]},{"given":"Alicia","family":"Barroso","sequence":"additional","affiliation":[{"name":"21Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain."}]},{"given":"Daniel","family":"Barrowdale","sequence":"additional","affiliation":[{"name":"5Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom."}]},{"given":"Muriel","family":"Belotti","sequence":"additional","affiliation":[{"name":"22Service de G\u00e9n\u00e9tique, Institut Curie, Paris, France."}]},{"given":"Javier","family":"Benitez","sequence":"additional","affiliation":[{"name":"23Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain."},{"name":"24Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain."}]},{"given":"Birgitte","family":"Bertelsen","sequence":"additional","affiliation":[{"name":"25Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark."}]},{"given":"Marinus J.","family":"Blok","sequence":"additional","affiliation":[{"name":"26Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands."}]},{"given":"Istvan","family":"Bodrogi","sequence":"additional","affiliation":[{"name":"27Department of Chemotherapy, National Institute of Oncology, Budapest, Hungary."}]},{"given":"Val\u00e9rie","family":"Bonadona","sequence":"additional","affiliation":[{"name":"28Unit\u00e9 de Pr\u00e9vention et d'Epid\u00e9miologie G\u00e9n\u00e9tique, Centre L\u00e9on B\u00e9rard, Lyon, France."}]},{"given":"Bernardo","family":"Bonanni","sequence":"additional","affiliation":[{"name":"29Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy."}]},{"given":"Davide","family":"Bondavalli","sequence":"additional","affiliation":[{"name":"29Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy."}]},{"given":"Susanne E.","family":"Boonen","sequence":"additional","affiliation":[{"name":"30Clinical Genetic Unit, Department of Paediatrics, Zealand University Hospital, Roskilde, Denmark."}]},{"given":"Julika","family":"Borde","sequence":"additional","affiliation":[{"name":"31Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany."},{"name":"32Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany."},{"name":"33Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany."}]},{"given":"Ake","family":"Borg","sequence":"additional","affiliation":[{"name":"34Department of Oncology, Lund University and Sk\u00e5ne University Hospital, Lund, Sweden."}]},{"given":"Angela R.","family":"Bradbury","sequence":"additional","affiliation":[{"name":"35Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania."}]},{"given":"Angela","family":"Brady","sequence":"additional","affiliation":[{"name":"36North West Thames Regional Genetics Service, Kennedy Galton Centre, The North West London Hospitals NHS Trust, Middlesex, United Kingdom."}]},{"given":"Carole","family":"Brewer","sequence":"additional","affiliation":[{"name":"37Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, United Kingdom."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-3512","authenticated-orcid":false,"given":"Joan","family":"Brunet","sequence":"additional","affiliation":[{"name":"38Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigaci\u00f3 Biom\u00e8dica de Girona), Catalan Institute of Oncology, CIBERONC, Girona, Spain."}]},{"given":"Bruno","family":"Buecher","sequence":"additional","affiliation":[{"name":"22Service de G\u00e9n\u00e9tique, Institut Curie, Paris, France."}]},{"given":"Saundra S.","family":"Buys","sequence":"additional","affiliation":[{"name":"39Department of Medicine, Huntsman Cancer Institute, Salt Lake City, Utah."}]},{"given":"Santiago","family":"Cabezas-Camarero","sequence":"additional","affiliation":[{"name":"40Department of Oncology, Hospital Clinico San Carlos, IdISSC, Madrid, Spain."}]},{"given":"Trinidad","family":"Cald\u00e9s","sequence":"additional","affiliation":[{"name":"41Medical Oncology Department, Hospital Cl\u00ednico San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Centro Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain."}]},{"given":"Almuth","family":"Caliebe","sequence":"additional","affiliation":[{"name":"42Institute of Human Genetics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0589-1829","authenticated-orcid":false,"given":"Maria A.","family":"Caligo","sequence":"additional","affiliation":[{"name":"43Section of Molecular Genetics, Department of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy."}]},{"given":"Mariarosaria","family":"Calvello","sequence":"additional","affiliation":[{"name":"29Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-4155","authenticated-orcid":false,"given":"Ian G.","family":"Campbell","sequence":"additional","affiliation":[{"name":"44Peter MacCallum Cancer Center, Melbourne, Victoria, Australia."},{"name":"45Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia."}]},{"given":"Ileana","family":"Carnevali","sequence":"additional","affiliation":[{"name":"46UO Anatomia Patologica, Ospedale di Circolo-Universit\u00e0 dell'Insubria, Varese, Italy."}]},{"given":"Estela","family":"Carrasco","sequence":"additional","affiliation":[{"name":"20High Risk and Cancer Prevention Group, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, Barcelona, Spain."}]},{"given":"Tsun L.","family":"Chan","sequence":"additional","affiliation":[{"name":"47Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Centre, Happy Valley, Hong Kong."},{"name":"48Department of Pathology, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong."}]},{"given":"Annie T.W.","family":"Chu","sequence":"additional","affiliation":[{"name":"47Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Centre, Happy Valley, Hong Kong."}]},{"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"name":"49Departments of Pediatrics and Medicine, Columbia University, New York, New York."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0841-7372","authenticated-orcid":false,"given":"Kathleen B.M.","family":"Claes","sequence":"additional","affiliation":[{"name":"50Centre for Medical Genetics, Ghent University, Ghent, Belgium."}]},{"given":"GEMO Study","family":"Collaborators","sequence":"additional","affiliation":[{"name":"22Service de G\u00e9n\u00e9tique, Institut Curie, Paris, France."}]},{"given":"EMBRACE","family":"Collaborators","sequence":"additional","affiliation":[{"name":"5Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom."}]},{"given":"Jackie","family":"Cook","sequence":"additional","affiliation":[{"name":"51Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom."}]},{"given":"Laura","family":"Cortesi","sequence":"additional","affiliation":[{"name":"52Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy."}]},{"given":"Fergus J.","family":"Couch","sequence":"additional","affiliation":[{"name":"53Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota."}]},{"given":"Mary B.","family":"Daly","sequence":"additional","affiliation":[{"name":"54Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania."}]},{"given":"Giuseppe","family":"Damante","sequence":"additional","affiliation":[{"name":"55Department of Medical and Biological Sciences, University of Udine, Udine, Italy."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7764-1397","authenticated-orcid":false,"given":"Esther","family":"Darder","sequence":"additional","affiliation":[{"name":"38Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigaci\u00f3 Biom\u00e8dica de Girona), Catalan Institute of Oncology, CIBERONC, Girona, Spain."}]},{"given":"Rosemarie","family":"Davidson","sequence":"additional","affiliation":[{"name":"56Department of Clinical Genetics, South Glasgow University Hospitals, Glasgow, United Kingdom."}]},{"given":"Miguel","family":"de la Hoya","sequence":"additional","affiliation":[{"name":"41Medical Oncology Department, Hospital Cl\u00ednico San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Centro Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain."}]},{"given":"Lara Della","family":"Puppa","sequence":"additional","affiliation":[{"name":"57Division of Functional Onco-genomics and Genetics, Centro di 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M.","family":"Domchek","sequence":"additional","affiliation":[{"name":"35Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania."}]},{"given":"Alan","family":"Donaldson","sequence":"additional","affiliation":[{"name":"61Clinical Genetics Department, St Michael's Hospital, Bristol, United Kingdom."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4981-7903","authenticated-orcid":false,"given":"Bernd","family":"Dworniczak","sequence":"additional","affiliation":[{"name":"62Institute of Human Genetics, University of M\u00fcnster, M\u00fcnster, Germany."}]},{"given":"Douglas F.","family":"Easton","sequence":"additional","affiliation":[{"name":"5Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom."},{"name":"63Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom."}]},{"given":"Diana M.","family":"Eccles","sequence":"additional","affiliation":[{"name":"64Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3698-6241","authenticated-orcid":false,"given":"Rosalind A.","family":"Eeles","sequence":"additional","affiliation":[{"name":"65Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, United Kingdom."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-3622","authenticated-orcid":false,"given":"Hans","family":"Ehrencrona","sequence":"additional","affiliation":[{"name":"66Department of Clinical Genetics, Lund University Hospital, Lund, Sweden."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8761-714X","authenticated-orcid":false,"given":"Bent","family":"Ejlertsen","sequence":"additional","affiliation":[{"name":"67Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark."}]},{"given":"Christoph","family":"Engel","sequence":"additional","affiliation":[{"name":"68Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany."},{"name":"69LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-5784","authenticated-orcid":false,"given":"D. 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