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Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Patel VL 1 , Busch EL 2 , Friebel TM 2 , Cronin A 3 , Leslie G 4 , McGuffog L 4 Show all authors , Adlard J 5 , Agata S 6 , Agnarsson BA 7 , Ahmed M 8 , Aittomäki K 9 , Alducci E 6 , Andrulis IL 10 , Arason A 7 , Arnold N 11 , Artioli G 12 , Arver B 13 , Auber B 14 , Azzollini J 15 , Balmaña J 16 , Barkardottir RB 7 , Barnes DR 4 , Barroso A 17 , Barrowdale D 4 , Belotti M 18 , Benitez J 19 , Bertelsen B 20 , Blok MJ 21 , Bodrogi I 22 , Bonadona V 23 , Bonanni B 24 , Bondavalli D 24 , Boonen SE 25 , Borde J 26 , Borg A 27 , Bradbury AR 28 , Brady A 29 , Brewer C 30 , Brunet J 31 , Buecher B 18 , Buys SS 32 , Cabezas-Camarero S 33 , Caldés T 34 , Caliebe A 35 , Caligo MA 36 , Calvello M 24 , Campbell IG 37 , Carnevali I 38 , Carrasco E 16 , Chan TL 39 , Chu ATW 39 , Chung WK 40 , Claes KBM 41 , Collaborators GS 18 , Collaborators E 4 , Cook J 42 , Cortesi L 43 , Couch FJ 44 , Daly MB 45 , Damante G 46 , Darder E 31 , Davidson R 47 , de la Hoya M 34 , Puppa LD 48 , Dennis J 4 , Díez O 49 , Ding YC 50 , Ditsch N 51 , Domchek SM 28 , Donaldson A 52 , Dworniczak B 53 , Easton DF 4 , Eccles DM 54 , Eeles RA 55 , Ehrencrona H 56 , Ejlertsen B 57 , Engel C 58 , Evans DG 59 , Faivre L 60 , Faust U 61 , Feliubadaló L 62 , Foretova L 63 , Fostira F 64 , Fountzilas G 65 , Frost D 4 , García-Barberán V 34 , Garre P 34 , Gauthier-Villars M 18 , Géczi L 22 , Gehrig A 66 , Gerdes AM 67 , Gesta P 68 , Giannini G 69 , Glendon G 10 , Godwin AK 70 , Goldgar DE 71 , Greene MH 72 , Gutierrez-Barrera AM 73 , Hahnen E 74 , Hamann U 75 , Hauke J 26 , Herold N 26 , Hogervorst FBL 76 , Honisch E 77 , Hopper JL 78 , Hulick PJ 79 , Investigators K 37 , Investigators H 80 , Izatt L 81 , Jager A 82 , James P 83 , Janavicius R 84 , Jensen UB 85 , Jensen TD 86 , Johannsson OT 87 , John EM 88 , Joseph V 89 , Kang E 90 , Kast K 91 , Kiiski JI 92 , Kim SW 93 , Kim Z 94 , Ko KP 95 , Konstantopoulou I 64 , Kramer G 96 , Krogh L 97 , Kruse TA 97 , Kwong A 39 , Larsen M 26 , Lasset C 23 , Lautrup C 98 , Lazaro C 62 , Lee J 99 , Lee JW 100 , Lee MH 99 , Lemke J 101 , Lesueur F 18 , Liljegren A 13 , Lindblom A 102 , Llovet P 34 , Lopez-Fernández A 16 , Lopez-Perolio I 34 , Lorca V 34 , Loud JT 72 , Ma ESK 39 , Mai PL 103 , Manoukian S 15 , Mari V 104 , Martin L 105 , Matricardi L 6 , Mebirouk N 18 , Medici V 43 , Meijers-Heijboer HEJ 106 , Meindl A 51 , Mensenkamp AR 107 , Miller C 108 , Gomes DM 109 , Montagna M 6 , Mooij TM 110 , Moserle L 6 , Mouret-Fourme E 18 , Mulligan AM 111 , Nathanson KL 28 , Navratilova M 63 , Nevanlinna H 92 , Niederacher D 78 , Nielsen FCC 20 , Nikitina-Zake L 112 , Offit K 90 , Olah E 113 , Olopade OI 114 , Ong KR 115 , Osorio A 19 , Ott CE 116 , Palli D 117 , Park SK 118 , Parsons MT 119 , Pedersen IS 120 , Peissel B 15 , Peixoto A 121 , Pérez-Segura P 33 , Peterlongo P 122 , Petersen AH 86 , Porteous ME 123 , Pujana MA 124 , Radice P 125 , Ramser J 126 , Rantala J 127 , Rashid MU 75 , Rhiem K 26 , Rizzolo P 69 , Robson ME 128 , Rookus MA 110 , Rossing CM 20 , Ruddy KJ 129 , Santos C 121 , Saule C 18 , Scarpitta R 130 , Schmutzler RK 74 , Schuster H 131 , Senter L 132 , Seynaeve CM 82 , Shah PD 28 , Sharma P 133 , Shin VY 134 , Silvestri V 69 , Simard J 135 , Singer CF 136 , Skytte AB 86 , Snape K 137 , Solano AR 138 , Soucy P 133 , Southey MC 139 , Spurdle AB 119 , Steele L 50 , Steinemann D 140 , Stoppa-Lyonnet D 18 , Stradella A 141 , Sunde L 85 , Sutter C 142 , Tan YY 143 , Teixeira MR 121 , Teo SH 144 , Thomassen M 97 , Tibiletti MG 38 , Tischkowitz M 145 , Tognazzo S 6 , Toland AE 146 , Tommasi S 147 , Torres D 75 , Toss A 43 , Trainer AH 148 , Tung N 149 , van Asperen CJ 150 , van der Baan FH 110 , van der Kolk LE 76 , van der Luijt RB 151 , van Hest LP 152 , Varesco L 153 , Varon-Mateeva R 116 , Viel A 48 , Vierstraete J 41 , Villa R 15 , von Wachenfeldt A 13 , Wagner P 154 , Wang-Gohrke S 155 , Wappenschmidt B 74 , Weitzel JN 156 , Wieme G 41 , Yadav S 129 , Yannoukakos D 64 , Yoon SY 157 , Zanzottera C 15 , Zorn KK 103 , D'Amico AV 1 , Freedman ML 3 , Pomerantz MM 3 , Chenevix-Trench G 119 , Antoniou AC 4 , Neuhausen SL 50 , Ottini L 69 , Nielsen HR 97 , Rebbeck TR 158

Affiliations 

  • 1 Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts
  • 2 Harvard T.H. Chan School of Public Health, Boston, Massachusetts
  • 3 Dana-Farber Cancer Institute. Boston, Massachusetts
  • 4 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
  • 5 Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, United Kingdom
  • 6 Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
  • 7 Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland
  • 8 North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom
  • 9 Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 10 Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada
  • 11 Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany
  • 12 ULSS 3 Serenissima, U.O.C. Oncologia ed Ematologia Oncologica, Mirano, Venice, Italy
  • 13 Department of Oncology, Karolinska Institutet, Stockholm, Sweden
  • 14 Institute of Human Genetics, Hannover Medical School, Hannover, Germany
  • 15 Unit 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
  • 16 High Risk and Cancer Prevention Group, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, Barcelona, Spain
  • 17 Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • 18 Service de Génétique, Institut Curie, Paris, France
  • 19 Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • 20 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 21 Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands
  • 22 Department of Chemotherapy, National Institute of Oncology, Budapest, Hungary
  • 23 Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France
  • 24 Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy
  • 25 Clinical Genetic Unit, Department of Paediatrics, Zealand University Hospital, Roskilde, Denmark
  • 26 Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany
  • 27 Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden
  • 28 Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
  • 29 North West Thames Regional Genetics Service, Kennedy Galton Centre, The North West London Hospitals NHS Trust, Middlesex, United Kingdom
  • 30 Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, United Kingdom
  • 31 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona), Catalan Institute of Oncology, CIBERONC, Girona, Spain
  • 32 Department of Medicine, Huntsman Cancer Institute, Salt Lake City, Utah
  • 33 Department of Oncology, Hospital Clinico San Carlos, IdISSC, Madrid, Spain
  • 34 Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
  • 35 Institute of Human Genetics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany
  • 36 Section of Molecular Genetics, Department of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy
  • 37 Peter MacCallum Cancer Center, Melbourne, Victoria, Australia
  • 38 UO Anatomia Patologica, Ospedale di Circolo-Università dell'Insubria, Varese, Italy
  • 39 Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Centre, Happy Valley, Hong Kong
  • 40 Departments of Pediatrics and Medicine, Columbia University, New York, New York
  • 41 Centre for Medical Genetics, Ghent University, Ghent, Belgium
  • 42 Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom
  • 43 Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy
  • 44 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
  • 45 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
  • 46 Department of Medical and Biological Sciences, University of Udine, Udine, Italy
  • 47 Department of Clinical Genetics, South Glasgow University Hospitals, Glasgow, United Kingdom
  • 48 Division of Functional Onco-genomics and Genetics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
  • 49 Oncogenetics Group, Clinical and Molecular Genetics Area, Vall d'Hebron Institute of Oncology (VHIO), University Hospital, Barcelona, Spain
  • 50 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California
  • 51 Department of Gynecology and Obstetrics, Ludwig Maximilian University of Munich, Munich, Germany
  • 52 Clinical Genetics Department, St Michael's Hospital, Bristol, United Kingdom
  • 53 Institute of Human Genetics, University of Münster, Münster, Germany
  • 54 Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
  • 55 Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, United Kingdom
  • 56 Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
  • 57 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 58 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
  • 59 Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health and Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
  • 60 Unité d'oncogénétique, Centre de Lutte Contre le Cancer, Centre Georges-François Leclerc, Dijon, France
  • 61 Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
  • 62 Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC, Barcelona, Spain
  • 63 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
  • 64 Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research "Demokritos", Athens, Greece
  • 65 Second Department of Medical Oncology, EUROMEDICA General Clinic of Thessaloniki, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece
  • 66 Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University of Würzburg, Würzburg, Germany
  • 67 Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark
  • 68 Service Régional Oncogénétique Poitou-Charentes, CH Niort, Niort, France
  • 69 Department of Molecular Medicine, University La Sapienza, Rome, Italy
  • 70 Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, Kansas
  • 71 Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah
  • 72 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
  • 73 Department of Breast Medical Oncology and Clinical Genetics Program, University of Texas MD Anderson Cancer Center, Houston, Texas
  • 74 Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
  • 75 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 76 Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
  • 77 Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
  • 78 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
  • 79 Center for Medical Genetics, NorthShore University HealthSystem, Evanston, Illinois
  • 80 The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Coordinating center: The Netherlands Cancer Institute, Amsterdam, the Netherlands
  • 81 Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
  • 82 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
  • 83 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
  • 84 Hematology, Oncology and Transfusion Medicine Center, Department of Molecular and Regenerative Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania
  • 85 Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
  • 86 Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark
  • 87 Department of Oncology, Landspitali University Hospital, Reykjavik, Iceland
  • 88 Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California
  • 89 Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York
  • 90 Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
  • 91 Department of Gynecology and Obstetrics, Technical University of Dresden, Dresden, Germany
  • 92 Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 93 Department of Surgery, Daerim Saint Mary's Hospital, Seoul, Korea
  • 94 Department of Surgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
  • 95 Department of Preventive Medicine, Gacheon University College of Medicine, Incheon, Republic of Korea
  • 96 Department of Urology, Medical University of Vienna, Vienna, Austria
  • 97 Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
  • 98 Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark
  • 99 Department of Surgery, Soonchunhyang University College of Medicine and Soonchunhyang University Hospital, Seoul, Korea
  • 100 Department of Surgery, Ulsan University College of Medicine and Asan Medical Center, Seoul, Korea
  • 101 Institute of Human Genetics, University Hospital Leipzig, Leipzig, Germany
  • 102 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  • 103 Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 104 Département d'Hématologie-Oncologie Médicale, Centre Antoine Lacassagne, Nice, France
  • 105 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom
  • 106 Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands
  • 107 Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
  • 108 Department of Clinical Genetics, Alder Hey Hospital, Liverpool, United Kingdom
  • 109 Service de Biologie de la Reproduction, Cytogénétique et Génétique Médicale, CHI Poissy - Saint Germain, Poissy, France
  • 110 Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
  • 111 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
  • 112 Latvian Biomedical Research and Study Centre, Riga, Latvia
  • 113 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
  • 114 Center for Clinical Cancer Genetics, The University of Chicago, Chicago, Illinois
  • 115 West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Birmingham, United Kingdom
  • 116 Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  • 117 Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
  • 118 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 119 Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  • 120 Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
  • 121 Department of Genetics, Portuguese Oncology Institute, Porto, Portugal
  • 122 Genome Diagnostics Program, IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  • 123 South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, United Kingdom
  • 124 Translational Research Laboratory, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC, Barcelona, Spain
  • 125 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, in Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy
  • 126 Division of Gynaecology and Obstetrics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
  • 127 Clinical Genetics, Karolinska Institutet, Stockholm, Sweden
  • 128 Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
  • 129 Department of Oncology, Mayo Clinic, Rochester, Minnesota
  • 130 Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, Pisa, Italy
  • 131 Unité d'Oncogénétique, Centre de Lutte Contre le Cancer Paul Strauss, Strasbourg, France
  • 132 Clinical Cancer Genetics Program, Division of Human Genetics, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
  • 133 Department of Internal Medicine, Division of Oncology, University of Kansas Medical Center, Westwood, Kansas
  • 134 Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong
  • 135 Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Centre, Québec City, Québec, Canada
  • 136 Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  • 137 Medical Genetics Unit, St George's, University of London, London, United Kingdom
  • 138 INBIOMED, Faculty of Medicine/CONICET and CEMIC, Department of Clinical Chemistry, Medical Direction, University of Buenos Aires, Buenos Aires, Argentina
  • 139 Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
  • 140 Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany
  • 141 Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC, Barcelona, Spain
  • 142 Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany
  • 143 Department of OB/GYN, Medical University of Vienna, Vienna, Austria
  • 144 Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia
  • 145 Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montréal, Quebec, Canada
  • 146 Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio
  • 147 Istituto Nazionale Tumori 'Giovanni Paolo II, Bari, Italy
  • 148 Parkville Familial Cancer Centre, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia
  • 149 Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 150 Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
  • 151 Department of Medical Genetics, University Medical Center, Utrecht, the Netherlands
  • 152 Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • 153 Unit of Hereditary Cancer, Department of Epidemiology, Prevention and Special Functions, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
  • 154 Department of Women's Health, Tubingen University Hospital, Tubingen, Germany
  • 155 Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany
  • 156 Clinical Cancer Genetics, City of Hope, Duarte, California
  • 157 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia
  • 158 Harvard T.H. Chan School of Public Health, Boston, Massachusetts. [email protected]
Cancer Res, 2020 Feb 01;80(3):624-638.
PMID: 31723001 DOI: 10.1158/0008-5472.CAN-19-1840

Abstract

Pathogenic 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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