Objective. Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. Methods. Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631-SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. Results. At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 x 10(-9)) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 x 10(-9)). SNP rs6902488 at 6p25.2 (r(2) = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 x 10(-8)). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 x 10(-7)) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 x 10(-7)). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 x 10(-7)). Conclusion. While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry. (C) 2019 Published by Elsevier Inc.
基金:
U.S. National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA1X01HG007491-01, U19-CA148112, R01-CA149429, R01-CA058598]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [MOP-86727]; Ovarian Cancer Research Fund (OCRF); European UnionEuropean Union (EU) [HEALTH -F2-2009-223175]; Cancer Research UKCancer Research UK [C1287/A10710, C1287/A10118, C12292/A11174, C490/A8339]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [U19-CA148112, R01-CA058598, R01 CA114343, RO1 CA149429, RO1 CA176016, RO1 CA128978, RO1 CA116167, RO1 CA176785, RO1 CA114343]; GAME -ON initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; NCI Specialized Program of Research Excellence (SPORE) in Breast CancerUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P50 CA116201]; Canadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR) [MOP 86727]; CIHR Team in Familial Risks of Breast CancerCanadian Institutes of Health Research (CIHR); Ministere de Itconomie, Innovation et Exportation du Quebec [PSR-SI1R1-701]; Komen Foundation for the CureSusan G. Komen Breast Cancer Foundation; Breast Cancer Research Foundation (BCRF); OCRF; National Health and Medical Research Council of AustraliaNational Health and Medical Research Council of Australia [1017028]; Wellcome TrustWellcome Trust [076113]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81320108022, 81502877]; Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) in ChinaProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT_14R40]; Tianjin Science and Technology Committee Foundation [16JCYBJC26600]; National Human Genetic Resources Sharing Service Platform [2005DKA21300]; National Key Research and Development program of China: The Net construction of human genetic resource Bio-bank in North China [2016YFC1201703]; NIH/National Center for Research Resources/General Clinical Research Center grant [M01-RR000056, K07-CA080668, R01-CA095023, P50CA159981]; National Center for Advancing Translational Sciences (NCATS)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000124]; National Institute of Environmental Health Sciences (NIEHS)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [Z01 ES044005]; Japanese Ministry of Education, Culture, Sports, Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [17015018, 221S0001]; JSPS KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [16H06277, 26253041]; Ministry of Health, Labour and WelfareMinistry of Health, Labour and Welfare, Japan; National Cancer Institute grants (U.S.A) [UM1 CA182910]; U.S. Department of Defense (DoD) Congressionally Directed Medical Research Program (CDMRP) [DAMD17-01-1-0729, DAMD17-021-0669, W81XWH-07-0449, DAMD17-02-1-0666, W81XWH-10-1-02802]; American Cancer Society (ACS) Early Detection ProfessorshipAmerican Cancer Society [SIOP06-258-01-COUN]; ACSAmerican Cancer Society [CRTG-00-196-01-CCE]; Lon V Smith Foundation [LVS-39420]; California Cancer Research Program [0001389 V-20170, 2110200]; K99/R00 Pathway to Independence Award from the NCI [ROOCA184415]; Sao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2015/07925-5, 2017/08211-1]; Breast Cancer Now; Institute of Cancer Research (ICR); Cambridge NIHR Biomedical Research CentreNational Institute for Health Research (NIHR); Cancer Research UK (CRUK) Cambridge Cancer Centre; CRUKCancer Research UK [C490/A10119, C490/A10124]; Eve Appeal (The Oak Foundation); NIHR University College London Hospitals Biomedical Research Centre; CRUK, Royal Marsden Hospital; National Health & Medical Research Council (NHMRC) of AustraliaNational Health and Medical Research Council of Australia [199600, 400281, 209057, 251533, 396414, 504715]; Cancer Council of New South WalesCancer Council New South Wales; Cancer Council of VictoriaCanadian Institutes of Health Research (CIHR)Cancer Council Victoria; Cancer Council of QueenslandCancer Council Queensland; Cancer Council of South AustraliaCancer Council South Australia; Cancer Council of TasmaniaCancer Council Tasmania; Cancer Foundation of Western AustraliaCancer Council Western Australia [191, 211, 182]; Cancer Council VictoriaCanadian Institutes of Health Research (CIHR)Cancer Council Victoria; Brisbane Women's Club; Cancer Institute NSW [11 iTRC/1-06, 12/RIG/1-17]; NHMRCNational Health and Medical Research Council of Australia; Canadian Institutes of Health Research grantCanadian Institutes of Health Research (CIHR) [MOP -86727]; Margaret Cancer Centre Foundation-Bridge for the Cure; BC Cancer Foundation; VGH & UBC Hospital Foundation; ELAN Funds of the University of Erlangen-Nuremberg; Nationaal Kankerplan; Institute de Salud Carlos IIIInstituto de Salud Carlos III [P1 12/01319]; Ministerio de Economia y CompetitividadSpanish Government [SAF2012-35779]; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research [01 GB 9401]; German Cancer Research Center (DKFZ)Helmholtz Association; European Union (European Social Fund -ESF)European Union (EU)European Social Fund (ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) -Research Funding Program of the General Secretariat for Research Technology [SYN11_10_19 NBCA]; Helsinki University Research Fund; Rudolf-Bartling Foundation; Radboud University Medical Centre; Herlev Hospitals Forskningsrad; Direktor Jacob Madsens og Hustru Olga Madsens fond; Arvid Nilssons fond; Gangsted fonden; Danish Cancer SocietyDanish Cancer Society; European Commission (DG-SANCO)European Commission Joint Research Centre; International Agency for Research on Cancer ([ARC); Danish Cancer Society (Denmark)Danish Cancer Society; Ligue Contre le Cancer (France); Institut Gustave Roussy (France); Mutuelle Generale de ['Education Nationale, Institut National de la Sante et de la Recherche Medicate (INSERM) (France); German Cancer Aid (Germany)Deutsche Krebshilfe; German Cancer Research Center (DKFZ) (Germany); Federal Ministry of Education and Research (BMBF) (Germany)Federal Ministry of Education & Research (BMBF); Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul CancroAIRC-Italy (Italy)Associazione Italiana per la Ricerca sul Cancro (AIRC); National Research Council (Italy)Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports (VWS) (The Netherlands)Netherlands Government; Netherlands Cancer Registry (NKR) (The Netherlands)Netherlands Government; LK Research Funds (The Netherlands)Netherlands Government; Dutch Prevention Funds (The Netherlands)Netherlands Government; Dutch ZON (Zorg Onderzoek Nederland) (The Netherlands)Netherlands Government; World Cancer Research Fund (WCRF) (The Netherlands)Netherlands GovernmentWorld Cancer Research Fund International (WCRF); Statistics Netherlands (The Netherlands)Netherlands Government; Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS) (Spain)Instituto de Salud Carlos III [P113/00061, P113/01162]; Regional Government of Andalucia (Spain)Junta de Andalucia; Regional Government of Basque Country (Spain); Regional Government of Asturias (Spain); Regional Government of Murcia (Spain); Regional Government of Navarra (Spain); ISCIII RETIC (Spain)Instituto de Salud Carlos III [RD06/0020]; Swedish Cancer Society (Sweden)Swedish Cancer Society; Swedish Research Council (Sweden)Swedish Research Council; County Council of Skane (Sweden); County Council of Vasterbotten (Sweden); CRUK (United Kingdom) [14136, C570/A16491, C8221/A19170]; Medical Research Council (MRC) (United Kingdom)Medical Research Council UK (MRC) [1000143, MR/M012190/1]; Roswell Park Cancer Institute Alliance Foundation; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; Fraternal Order of Eagles; OHSU Foundation; Intramural Research Program of the National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI); Henry Ford Hospital; RBH [APP1025142, 310670, 628903]; [ERC-2009-AdG 232997]; [ULTR000445]; [R01-CA112523]; [R01-CA087538]; [N01-CN55424]; [N01 -PC -67001]; [R01CA122443]; [P30-CA15083]; [P50-CA136393]; [R01CA054281]; [R01-CA164973]; [R01-CA063464]; [R01-CA114343]; [R01-CA076016]; [R01-CA054419]; [P50-CA105009]; [R01-CA067262]; [UM1 CA176726]; [UM1 CA186107]; [P01 CA087969]; [RO1 CA049449]; [R01CA160669]; [P50 CA159981]; [R01CA126841]; [U01-CA071966]; [R01-CA016056]; [U01-CA069417]; [RO1 CA063678]; [RO1 CA063682]; [R01CA058860]; [P01CA17054]; [P30CA014089]; [R01CA061132]; [NO1PC67010]; [R03CA113148]; [R03CA115195]; [N01CN025403]
第一作者机构:[1]Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, 8700 Beverly Blvd,Suite 290W, Los Angeles, CA 90048 USA[2]Cedars Sinai Med Ctr, Cedars Sinai Genom Core, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA[*1]Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
共同第一作者:
通讯作者:
通讯机构:[1]Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, 8700 Beverly Blvd,Suite 290W, Los Angeles, CA 90048 USA[2]Cedars Sinai Med Ctr, Cedars Sinai Genom Core, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA[*1]Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
推荐引用方式(GB/T 7714):
Lawrenson Kate,Song Fengju,Hazelett Dennis J.,et al.Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women[J].GYNECOLOGIC ONCOLOGY.2019,153(2):343-355.doi:10.1016/j.ygyno.2019.02.023.
APA:
Lawrenson, Kate,Song, Fengju,Hazelett, Dennis J.,Kar, Siddhartha P.,Tyrer, Jonathan...&Goodman, Marc T..(2019).Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.GYNECOLOGIC ONCOLOGY,153,(2)
MLA:
Lawrenson, Kate,et al."Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women".GYNECOLOGIC ONCOLOGY 153..2(2019):343-355