title: Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.
abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
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authors.identifier: http://orcid.org/0000-0001-9726-603X
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authors.affiliation: Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
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authors.affiliation: Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
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authors.affiliation: Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
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authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA.
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authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
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authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt School of Medicine, Nashville, Tennessee, USA.|Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt Medical School, Nashville, Tennessee, USA.|Institute for Medicine and Public Health, Vanderbilt School of Medicine, Nashville, Tennessee, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt School of Medicine, Nashville, Tennessee, USA.
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authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
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authors.affiliation: Department of Gynecology and Obstetrics, Universtiy Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg, Erlangen, Germany.|Division of Hematology and Oncology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
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authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK.
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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authors.initials: RT
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authors.affiliation: Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, Athens, Greece.
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authors.initials: F
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authors.forename: William D
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authors.initials: BL
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authors.affiliation: Harvard T.H. Chan School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Friebel
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Chaim Sheba Medical Center, Ramat Gan, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Eitan
authors.initials: E
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Debra
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authors.affiliation: Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, UCLA Schools of Medicine and Public Health, Los Angeles, California, USA.
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authors.initials: A
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authors.affiliation: Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain.
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authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
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authors.affiliation: Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
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authors.initials: LM
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authors.affiliation: Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
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authors.initials: AM
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authors.initials: E
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authors.initials: MA
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authors.initials: J
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authors.initials: C
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authors.affiliation: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO) and Center for Molecular Medicine Cologne (CMMC), University Hospital Cologne, Cologne, Germany.
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authors.initials: C
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authors.initials: JH
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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authors.initials: A
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authors.initials: IB
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authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
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authors.initials: MJ
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authors.initials: L
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authors.initials: N
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authors.affiliation: Département Oncologie Génétique, Institut Paoli-Calmettes, Marseille, France.
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authors.initials: Z
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authors.affiliation: Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
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authors.initials: G
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authors.initials: R
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authors.initials: AJ
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authors.initials: L
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authors.initials: MK
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authors.initials: MR
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authors.affiliation: Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia.|University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia.
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authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
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authors.initials: LCV
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authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
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authors.initials: A
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authors.initials: RC
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authors.initials: A
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authors.initials: N
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authors.initials: D
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authors.initials: AH
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authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
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authors.initials: RB
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authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
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authors.initials: E
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authors.affiliation: Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, Pretoria, South Africa.
authors.forename: Elizabeth J
authors.initials: EJ
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authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
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authors.initials: A
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authors.affiliation: Institute of Medical and Human Genetics, Charité Universitätsmedizin, Campus Virchov Klinikum, Berlin, Germany.
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authors.initials: R
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authors.affiliation: Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain.|Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.
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authors.initials: A
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authors.affiliation: Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt Medical School, Nashville, Tennessee, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt School of Medicine, Nashville, Tennessee, USA.|Vanderbilt Genetics Institute and Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
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authors.initials: DV
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authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
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authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, Minnesota, USA.
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authors.initials: RA
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authors.initials: A
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authors.affiliation: Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK.
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authors.initials: L
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authors.affiliation: Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
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authors.initials: C
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authors.affiliation: Institute of Human Genetics, University Hospital, Leipzig, Germany.
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authors.initials: D
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authors.affiliation: Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.
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authors.initials: S
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authors.affiliation: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO) and Center for Molecular Medicine Cologne (CMMC), University Hospital Cologne, Cologne, Germany.
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authors.initials: PM
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authors.initials: CR
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authors.affiliation: Clinical Cancer Genetics, City of Hope, Duarte, California, USA.
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
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authors.initials: N
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authors.affiliation: Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, California, USA.|Department of Data Management Science, Stanford University School of Medicine, Stanford, California, USA.
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authors.initials: AS
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authors.affiliation: Departments of Human Genetics and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
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authors.initials: JT
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authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
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authors.initials: A
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authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.|British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
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authors.affiliation: Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
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authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA.
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authors.initials: AH
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, Athens, Greece.
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authors.initials: D
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authors.affiliation: Department of Epidemiology, University of California-Irvine, Irvine, California, USA.
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authors.affiliation: Magee-Womens Hospital of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Zorn
authors.affiliation: Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.|Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.affiliation: Center for Genomic Medicine, Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.affiliation: School of Women's and Children's Health, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.|Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
authors.affiliation: Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.|Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.affiliation: Department of Preventive Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea.|Seoul National University Cancer Research Institute, Seoul, Republic of Korea.|Department of Biomedical Science, Graduate School, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.affiliation: Clinical Genetics Research Laboratory, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.affiliation: Genomics Center, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City, Quebec, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
authors.affiliation: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO) and Center for Molecular Medicine Cologne (CMMC), University Hospital Cologne, Cologne, Germany.
authors.forename: Rita Katharina
authors.initials: RK
authors.lastname: Schmutzler
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Hazelett
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Alvaro N
authors.initials: AN
authors.lastname: Monteiro
authors.affiliation: Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.affiliation: Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.affiliation: Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.affiliation: Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.|Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.|Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors.forename: Paul D P
authors.identifier: http://orcid.org/0000-0001-8494-732X
authors.initials: PDP
authors.lastname: Pharoah
mesh_terms: D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D034501:Telomere-Binding Proteins / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C544946:Stn1 protein, human; D034501:Telomere-Binding Proteins