title: Identification of six new susceptibility loci for invasive epithelial ovarian cancer.
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.
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authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Shanghai Cancer Institute, Shanghai, China.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
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: Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: McLaughlin
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: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Alvaro N
authors.identifier: 0000000284484801
authors.initials: AN
authors.lastname: Monteiro
authors.affiliation: Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Permuth-Wey
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Ya-Yu
authors.initials: YY
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authors.affiliation: Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, University of California-Irvine, Irvine, California, USA.
authors.forename: Argyrios
authors.identifier: 0000000345293727
authors.initials: A
authors.lastname: Ziogas
authors.affiliation: Department of Epidemiology, University of California-Irvine, Irvine, California, USA.
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.affiliation: Women's Cancer, University College London Elizabeth Garrett Anderson (EGA) Institute for Women's Health, London, UK.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.affiliation: Women's Cancer, University College London Elizabeth Garrett Anderson (EGA) Institute for Women's Health, London, UK.
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.affiliation: Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors.forename: Patricia
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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: AW
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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.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: MC
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authors.affiliation: Department of Obstetrics, Gynecology and Oncology, 2nd Faculty of Medicine, Warsaw Medical University and Brodnowski Hospital, Warsaw, Poland.
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authors.initials: IK
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authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
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authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
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authors.affiliation: Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
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authors.initials: PP
authors.lastname: Pharoah
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
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authors.initials: AC
authors.lastname: Antoniou
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mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012306:Risk; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein