Fulltext

Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Kuchenbaecker KB 1 , Ramus SJ 2 , Tyrer J 3 , Lee A 1 , Shen HC 2 , Beesley J 4 Show all authors , Lawrenson K 2 , McGuffog L 1 , Healey S 4 , Lee JM 2 , Spindler TJ 2 , Lin YG 5 , Pejovic T 6 , Bean Y 6 , Li Q 7 , Coetzee S 8 , Hazelett D 9 , Miron A 10 , Southey M 11 , Terry MB 12 , Goldgar DE 13 , Buys SS 14 , Janavicius R 15 , Dorfling CM 16 , van Rensburg EJ 16 , Neuhausen SL 17 , Ding YC 17 , Hansen TV 18 , Jønson L 18 , Gerdes AM 19 , Ejlertsen B 20 , Barrowdale D 1 , Dennis J 21 , Benitez J 22 , Osorio A 23 , Garcia MJ 23 , Komenaka I 24 , Weitzel JN 25 , Ganschow P 26 , Peterlongo P 27 , Bernard L 28 , Viel A 29 , Bonanni B 30 , Peissel B 31 , Manoukian S 31 , Radice P 32 , Papi L 33 , Ottini L 34 , Fostira F 35 , Konstantopoulou I 35 , Garber J 36 , Frost D 1 , Perkins J 1 , Platte R 1 , Ellis S 1 , EMBRACE , Godwin AK 37 , Schmutzler RK 38 , Meindl A 39 , Engel C 40 , Sutter C 41 , Sinilnikova OM 42 , GEMO Study Collaborators , Damiola F 43 , Mazoyer S 43 , Stoppa-Lyonnet D 44 , Claes K 45 , De Leeneer K 45 , Kirk J 46 , Rodriguez GC 47 , Piedmonte M 48 , O'Malley DM 49 , de la Hoya M 50 , Caldes T 50 , Aittomäki K 51 , Nevanlinna H 52 , Collée JM 53 , Rookus MA 54 , Oosterwijk JC 55 , Breast Cancer Family Registry , Tihomirova L 56 , Tung N 57 , Hamann U 58 , Isaccs C 59 , Tischkowitz M 60 , Imyanitov EN 61 , Caligo MA 62 , Campbell IG 63 , Hogervorst FB 64 , HEBON , Olah E 65 , Diez O 66 , Blanco I 67 , Brunet J 68 , Lazaro C 69 , Pujana MA 69 , Jakubowska A 70 , Gronwald J 70 , Lubinski J 70 , Sukiennicki G 70 , Barkardottir RB 71 , Plante M 72 , Simard J 73 , Soucy P 73 , Montagna M 74 , Tognazzo S 74 , Teixeira MR 75 , KConFab Investigators , Pankratz VS 76 , Wang X 77 , Lindor N 76 , Szabo CI 78 , Kauff N 79 , Vijai J 79 , Aghajanian CA 79 , Pfeiler G 80 , Berger A 80 , Singer CF 80 , Tea MK 80 , Phelan CM 81 , Greene MH 82 , Mai PL 82 , Rennert G 83 , Mulligan AM 84 , Tchatchou S 85 , Andrulis IL 86 , Glendon G 85 , Toland AE 87 , Jensen UB 88 , Kruse TA 89 , Thomassen M 89 , Bojesen A 90 , Zidan J 91 , Friedman E 92 , Laitman Y 92 , Soller M 93 , Liljegren A 94 , Arver B 94 , Einbeigi Z 95 , Stenmark-Askmalm M 96 , Olopade OI 97 , Nussbaum RL 98 , Rebbeck TR 99 , Nathanson KL 99 , Domchek SM 99 , Lu KH 100 , Karlan BY 101 , Walsh C 101 , Lester J 101 , Australian Cancer Study (Ovarian Cancer Investigators) , Australian Ovarian Cancer Study Group , Hein A 102 , Ekici AB 103 , Beckmann MW 102 , Fasching PA 104 , Lambrechts D 105 , Van Nieuwenhuysen E 106 , Vergote I 106 , Lambrechts S 106 , Dicks E 3 , Doherty JA 107 , Wicklund KG 108 , Rossing MA 109 , Rudolph A 110 , Chang-Claude J 110 , Wang-Gohrke S 111 , Eilber U 110 , Moysich KB 112 , Odunsi K 113 , Sucheston L 112 , Lele S 112 , Wilkens LR 114 , Goodman MT 115 , Thompson PJ 115 , Shvetsov YB 114 , Runnebaum IB 116 , Dürst M 116 , Hillemanns P 117 , Dörk T 118 , Antonenkova N 119 , Bogdanova N 118 , Leminen A 52 , Pelttari LM 52 , Butzow R 120 , Modugno F 121 , Kelley JL 122 , Edwards RP 123 , Ness RB 124 , du Bois A 125 , Heitz F 125 , Schwaab I 126 , Harter P 125 , Matsuo K 127 , Hosono S 128 , Orsulic S 101 , Jensen A 129 , Kjaer SK 130 , Hogdall E 131 , Hasmad HN 132 , Azmi MA 133 , Teo SH 134 , Woo YL 135 , Fridley BL 136 , Goode EL 76 , Cunningham JM 77 , Vierkant RA 137 , Bruinsma F 138 , Giles GG 138 , Liang D 139 , Hildebrandt MA 140 , Wu X 140 , Levine DA 141 , Bisogna M 141 , Berchuck A 142 , Iversen ES 143 , Schildkraut JM 144 , Concannon P 145 , Weber RP 146 , Cramer DW 147 , Terry KL 147 , Poole EM 148 , Tworoger SS 148 , Bandera EV 149 , Orlow I 150 , Olson SH 150 , Krakstad C 151 , Salvesen HB 151 , Tangen IL 151 , Bjorge L 151 , van Altena AM 152 , Aben KK 153 , Kiemeney LA 154 , Massuger LF 152 , Kellar M 6 , Brooks-Wilson A 155 , Kelemen LE 156 , Cook LS 157 , Le ND 158 , Cybulski C 159 , Yang H 160 , Lissowska J 161 , Brinton LA 160 , Wentzensen N 160 , Hogdall C 162 , Lundvall L 162 , Nedergaard L 163 , Baker H 3 , Song H 3 , Eccles D 164 , McNeish I 165 , Paul J 166 , Carty K 166 , Siddiqui N 167 , Glasspool R 166 , Whittemore AS 168 , Rothstein JH 168 , McGuire V 168 , Sieh W 168 , Ji BT 160 , Zheng W 169 , Shu XO 169 , Gao YT 170 , Rosen B 171 , Risch HA 172 , McLaughlin JR 173 , Narod SA 174 , Monteiro AN 81 , Chen A 175 , Lin HY 175 , Permuth-Wey J 81 , Sellers TA 81 , Tsai YY 81 , Chen Z 175 , Ziogas A 176 , Anton-Culver H 176 , Gentry-Maharaj A 177 , Menon U 177 , Harrington P 3 , Lee AW 2 , Wu AH 2 , Pearce CL 2 , Coetzee G 9 , Pike MC 178 , Dansonka-Mieszkowska A 179 , Timorek A 180 , Rzepecka IK 179 , Kupryjanczyk J 179 , Freedman M 7 , Noushmehr H 181 , Easton DF 1 , Offit K 79 , Couch FJ 182 , Gayther S 2 , Pharoah PP 3 , Antoniou AC 1 , Chenevix-Trench G 4 , Consortium of Investigators of Modifiers of BRCA1 and BRCA2

Affiliations 

  • 1 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • 2 Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA
  • 3 Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
  • 4 Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  • 5 Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California, USA
  • 6 1] Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, USA. [2] Knight Cancer Institute, Portland, Oregon, USA
  • 7 Department of Medical Oncology, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
  • 8 1] Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. [2] Center for Cell-Based Therapy, Monte Alegre, Ribeirão Preto, Brazil. [3] Center for Integrative Systems Biology, Monte Alegre, Ribeirão Preto, Brazil
  • 9 1] Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA. [2] Department of Urology, University of Southern California, Los Angeles, California, USA
  • 10 Department of Genomics and Genome Sciences, Case Western Reserve University Medical School, Cleveland, Ohio, USA
  • 11 Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
  • 12 Department of Epidemiology, Columbia University, New York, New York, USA
  • 13 Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
  • 14 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA
  • 15 1] Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medical Center, Vilinius University Hospital Santariskiu Clinics, Vilnius, Lithuania, Vilnius University Hospital Santariskiu Clinics, Hematology, Oncology and Transfusion Medicine Center, Department of Molecular and Regenerative Medicine, Vilnius, Lithuania. [2] State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
  • 16 Department of Genetics, University of Pretoria, Pretoria, South Africa
  • 17 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, USA
  • 18 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 19 Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 20 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 21 1] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [2] Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
  • 22 1] Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), Madrid, Spain. [2] Human Genotyping Unit (CEGEN), Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), Madrid, Spain. [3] Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain
  • 23 1] Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), Madrid, Spain. [2] Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain
  • 24 Maricopa Medical Center, care of City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California, USA
  • 25 Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California, USA
  • 26 Cook County Health and Hospital System, care of City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California, USA
  • 27 Fondazione Istituto FIRC (Italian Foundation for Cancer Research) di Oncologia Molecolare (IFOM), Milan, Italy
  • 28 1] Department of Experimental Oncology, Istituto Europeo di Oncologia, Milan, Italy. [2] Cogentech Cancer Genetic Test Laboratory, Milan, Italy
  • 29 Division of Experimental Oncology, CRO (Centro di Riferimento Oncologico) Aviano National Cancer Institute, Aviano, Italy
  • 30 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy
  • 31 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico (Italian Research Hospital)) Istituto Nazionale Tumori (INT), Milan, Italy
  • 32 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy
  • 33 Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
  • 34 Department of Molecular Medicine, University La Sapienza, Rome, Italy
  • 35 Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology), National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, Athens, Greece
  • 36 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
  • 37 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
  • 38 1] Center for Hereditary Breast and Ovarian Cancer, Medical Faculty, University Hospital Cologne, Cologne, Germany. [2] Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany. [3] Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. [4] On behalf of the German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC)
  • 39 Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
  • 40 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
  • 41 Institute of Human Genetics, University Heidelberg, Heidelberg, Germany
  • 42 1] INSERM U1052, CNRS UMR 5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France. [2] Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon-Centre Léon Bérard, Lyon, France
  • 43 INSERM U1052, CNRS UMR 5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France
  • 44 1] Institut Curie, Department of Tumour Biology, Paris, France. [2] Institut Curie, INSERM U830, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France
  • 45 Center for Medical Genetics, Ghent University, Ghent, Belgium
  • 46 Australia New Zealand Gynecologic Oncology Group (ANZGOG) and Familial Cancer Service, Westmead Hosptial, Sydney, New South Wales, Australia
  • 47 Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois, USA
  • 48 Gynecologic Oncology Group, Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York, USA
  • 49 James Cancer Center, Ohio State University, Columbus, Ohio, USA
  • 50 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain
  • 51 Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland
  • 52 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
  • 53 Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 54 Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
  • 55 Department of Genetics, University Medical Center, Groningen University, Groningen, the Netherlands
  • 56 Latvian Biomedical Research and Study Centre, Riga, Latvia
  • 57 Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  • 58 Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
  • 59 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
  • 60 Program in Cancer Genetics, McGill University, Montreal, Quebec, Canada
  • 61 N.N. Petrov Institute of Oncology, St. Petersburg, Russia
  • 62 Section of Genetic Oncology, Department of Laboratory Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy
  • 63 VBCRC (Victorian Breast Cancer Research Consortium) Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  • 64 Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands
  • 65 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
  • 66 Oncogenetics Group, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, Barcelona, Spain
  • 67 Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute)-Catalan Institute of Oncology, Barcelona, Spain
  • 68 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona)-Catalan Institute of Oncology, Girona, Spain
  • 69 Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain
  • 70 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 71 Department of Pathology, Landspitali University Hospital and Biomedical Centre (BMC), Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  • 72 Gynaecologic Oncology Service, Centre Hospitalier Universitaire de Québec (CHUQ), Quebec City, Quebec, Canada
  • 73 Centre Hospitalier Universitaire de Québec (CHUQ) Research Center, Laval University, Quebec City, Quebec, Canada
  • 74 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto (IOV)-IRCCS, Padua, Italy
  • 75 1] Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal. [2] Department of Genetics, Portuguese Oncology Institute, Porto, Portugal
  • 76 Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
  • 77 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
  • 78 National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA
  • 79 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  • 80 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  • 81 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA
  • 82 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Rockville, Maryland, USA
  • 83 Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel
  • 84 1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. [2] Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
  • 85 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada
  • 86 1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
  • 87 Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, Ohio, USA
  • 88 Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
  • 89 Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
  • 90 Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark
  • 91 Institute of Oncology, Rivka Ziv Medical Center, Zefat, Israel
  • 92 Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel Aviv, Israel
  • 93 Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
  • 94 Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
  • 95 Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 96 Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
  • 97 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois, USA
  • 98 Department of Medicine and Genetics, University of California, San Francisco, San Francisco, California, USA
  • 99 Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  • 100 Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • 101 Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
  • 102 Department of Obstetrics and Gynecology, Erlangen University Hospital, University of Erlangen-Nuremberg, Erlangen, Germany
  • 103 Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany
  • 104 1] Department of Obstetrics and Gynecology, Erlangen University Hospital, University of Erlangen-Nuremberg, Erlangen, Germany. [2] Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
  • 105 1] Vesalius Research Center, VIB, Leuven, Belgium. [2] Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium
  • 106 Division of Gynecological Oncology, Department of Oncology, University Hospitals Leuven, Leuven, Belgium
  • 107 Department of Community and Family Medicine, Section of Biostatistics and Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA
  • 108 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  • 109 1] Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington, USA
  • 110 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 111 Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany
  • 112 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA
  • 113 Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA
  • 114 Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA
  • 115 1] Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. [2] Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
  • 116 Department of Gynecology, Jena University Hospital-Friedrich Schiller University, Jena, Germany
  • 117 Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany
  • 118 Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
  • 119 Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N., Minsk, Belarus
  • 120 1] Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. [2] Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland
  • 121 1] Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. [2] Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. [3] Ovarian Cancer Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. [4] Women's Cancer Research Program, Magee-Women's Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
  • 122 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • 123 1] Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. [2] Ovarian Cancer Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • 124 University of Texas School of Public Health, Houston, Texas, USA
  • 125 1] Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany. [2] Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany
  • 126 Institut für Humangenetik Wiesbaden, Wiesbaden, Germany
  • 127 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan
  • 128 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 129 Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
  • 130 1] Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. [2] Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 131 1] Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. [2] Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
  • 132 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia
  • 133 Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia
  • 134 1] Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia. [2] University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia
  • 135 1] Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia. [2] University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia
  • 136 Biostatistics and Informatics Shared Resource, University of Kansas Medical Center, Kansas City, Kansas, USA
  • 137 Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
  • 138 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia
  • 139 College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA
  • 140 Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • 141 Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  • 142 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA
  • 143 Department of Statistical Science, Duke University, Durham, North Carolina, USA
  • 144 1] Cancer Control and Population Sciences, Duke Cancer Institute, Durham, North Carolina, USA. [2] Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, USA
  • 145 1] Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USA. [2] Genetics Institute, University of Florida, Gainesville, Florida, USA
  • 146 Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, USA
  • 147 1] Harvard School of Public Health, Boston, Massachusetts, USA. [2] Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  • 148 1] Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  • 149 Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
  • 150 Department of Epidemiology and Biostatistics, Epidemiology Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  • 151 1] Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, Bergen, Norway. [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
  • 152 Department of Gynaecology, Radboud University Medical Centre, Nijmegen, the Netherlands
  • 153 1] Comprehensive Cancer Center The Netherlands, Utrecht, the Netherlands. [2] Department for Health Evidence, Radboud University Medical Centre, Nijmegen, the Netherlands
  • 154 1] Department for Health Evidence, Radboud University Medical Centre, Nijmegen, the Netherlands. [2] Department of Urology, Radboud University Medical Centre, Nijmegen, the Netherlands
  • 155 1] Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
  • 156 Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
  • 157 Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA
  • 158 Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
  • 159 International Hereditary Cancer Center, Department of Genetics and Pathology, Clinic of Opthalmology, Pomeranian Medical University, Szczecin, Poland
  • 160 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  • 161 Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
  • 162 Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 163 Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 164 Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
  • 165 Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, UK
  • 166 Cancer Research UK Clinical Trials Unit, Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK
  • 167 Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow, UK
  • 168 Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, California, USA
  • 169 Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  • 170 Shanghai Cancer Institute, Shanghai, China
  • 171 1] Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. [2] Department of Gynecologic-Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada
  • 172 Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA
  • 173 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  • 174 Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada
  • 175 Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida, USA
  • 176 Department of Epidemiology, University of California-Irvine, Irvine, California, USA
  • 177 Women's Cancer, University College London Elizabeth Garrett Anderson (EGA) Institute for Women's Health, London, UK
  • 178 1] Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA. [2] Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  • 179 Department of Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
  • 180 Department of Obstetrics, Gynecology and Oncology, 2nd Faculty of Medicine, Warsaw Medical University and Brodnowski Hospital, Warsaw, Poland
  • 181 Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
  • 182 1] Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [2] Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
Nat Genet, 2015 Feb;47(2):164-71.
PMID: 25581431 DOI: 10.1038/ng.3185

Abstract

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

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

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