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.
[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;
[3]Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjin, Peoples R China;
[4]Dept Epidemiol & Biostat, Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China;
[5]Univ Cambridge, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England;
[6]H Lee Moffitt Canc Ctr & Res Inst, Dept Gynecol Oncol, Tampa, FL USA;
[7]H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA;
[8]Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA;
[9]Univ Southern Calif, Keck Sch Med, Dept Prevent Med, 1450 Biggy St, Los Angeles, CA USA;
[10]Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Sao Paulo, Brazil;
[11]Baylor Sch Med, Dept Med, Inst Clin & Translat Res, Houston, TX USA;
[12]Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol, Honolulu, HI 96822 USA;
[13]QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, 300 Herston Rd, Herston, Qld 4006, Australia;
[14]Seoul Natl Univ, Dept Prevent Med, Coll Med, Seoul, South Korea;
[15]Seoul Natl Univ, Canc Res Inst, Seoul, South Korea;
[16]Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea;
[17]Univ Utah, Dept Populat Hlth Sci, Canc Res Huntsman Canc Inst, Salt Lake City, UT 84112 USA;
[18]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol Southern China, Guangzhou 510060, Guangdong, Peoples R China;
[19]ShanghaiBio Corp, Shanghai, Peoples R China;
[20]CloudHlth Genom Ltd, Shanghai, Peoples R China;
[21]Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea;
[22]BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada;
[23]Seoul Natl Univ, Grad Sch, Dept Biomed Sci, 103 Daehak Ro, Seoul 110799, South Korea;
[24]Univ Malaya, Dept Obstet & Gynaecol, Fac Med, Kuala Lumpur, Malaysia;
[25]Aichi Canc Ctr Hosp, Dept Gynecol Oncol, Nagoya, Aichi, Japan;
[26]Coll Med, Dept Prevent Med, Seoul, South Korea;
[27]Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA;
[28]Hebei Med Univ, Hosp 4, Dept Obstet & Gynaecol, Shijiazhuang, Hebei, Peoples R China;
[29]Shanghai Jiao Tong Univ, Minist Educ, BioX Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai, Peoples R China;
[30]Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol,Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA;
[31]Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA;
[32]Peter MacCallum Canc Inst, Melbourne, Vic, Australia;
[33]Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA;
[34]Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA;
[35]Fudan Univ, Shanghai Canc Ctr, Inst Canc, Shanghai 200032, Peoples R China;
[36]Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC 27710 USA;
[37]Hebei Med Univ, Hosp 4, Dept Mol Biol, Shijiazhuang, Hebei, Peoples R China;
[38]Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA;
[39]Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA;
[40]Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA;
[41]Canc Res Initiat Fdn, Subang Jaya, Selangor, Malaysia;
[42]Aichi Canc Ctr Res Inst, Div Mol & Clin Epidemiol, Nagoya, Aichi, Japan;
[43]Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Strangeways Res Lab, Worts Causeway, Cambridge, England;
[44]Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA
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