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Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.


ABSTRACT: 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?×?10-9) and high-grade serous EOC (HGSOC) (OR?=?1.34, P?=?4.3?×?10-9). SNP rs6902488 at 6p25.2 (r2?=?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?×?10-8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR?=?1.33, P?=?1.2?×?10-7) and rs74917072 at chromosome 2q37.3 (OR?=?1.25, P?=?4.7?×?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?×?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.

SUBMITTER: Lawrenson K 

PROVIDER: S-EPMC6754211 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.

Lawrenson Kate K   Song Fengju F   Hazelett Dennis J DJ   Kar Siddhartha P SP   Tyrer Jonathan J   Phelan Catherine M CM   Corona Rosario I RI   Rodríguez-Malavé Norma I NI   Seo Ji-Hei JH   Adler Emily E   Coetzee Simon G SG   Segato Felipe F   Fonseca Marcos A S MAS   Amos Christopher I CI   Carney Michael E ME   Chenevix-Trench Georgia G   Choi Jiyeob J   Doherty Jennifer A JA   Jia Weihua W   Jin Gang J GJ   Kim Byoung-Gie BG   Le Nhu D ND   Lee Juyeon J   Li Lian L   Lim Boon K BK   Adenan Noor A NA   Mizuno Mika M   Park Boyoung B   Pearce Celeste L CL   Shan Kang K   Shi Yongyong Y   Shu Xiao-Ou XO   Sieh Weiva W   Thompson Pamela J PJ   Wilkens Lynne R LR   Wei Qingyi Q   Woo Yin L YL   Yan Li L   Karlan Beth Y BY   Freedman Matthew L ML   Noushmehr Houtan H   Goode Ellen L EL   Berchuck Andrew A   Sellers Thomas A TA   Teo Soo-Hwang SH   Zheng Wei W   Matsuo Keitaro K   Park Sue S   Chen Kexin K   Pharoah Paul D P PDP   Gayther Simon A SA   Goodman Marc T MT  

Gynecologic oncology 20190319 2


<h4>Objective</h4>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.<h4>Methods</h4>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 unaffect  ...[more]

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