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

Publication ,  Journal Article
Lawrenson, K; Song, F; Hazelett, DJ; Kar, SP; Tyrer, J; Phelan, CM; Corona, RI; Rodríguez-Malavé, NI; Seo, J-H; Adler, E; Coetzee, SG; Choi, J ...
Published in: Gynecol Oncol
May 2019

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.

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Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

May 2019

Volume

153

Issue

2

Start / End Page

343 / 355

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Case-Control Studies
  • Carcinoma, Ovarian Epithelial
  • Base Sequence
 

Citation

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Lawrenson, K., Song, F., Hazelett, D. J., Kar, S. P., Tyrer, J., Phelan, C. M., … Goodman, M. T. (2019). Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women. Gynecol Oncol, 153(2), 343–355. https://doi.org/10.1016/j.ygyno.2019.02.023
Lawrenson, Kate, Fengju Song, Dennis J. Hazelett, Siddhartha P. Kar, Jonathan Tyrer, Catherine M. Phelan, Rosario I. Corona, et al. “Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.Gynecol Oncol 153, no. 2 (May 2019): 343–55. https://doi.org/10.1016/j.ygyno.2019.02.023.
Lawrenson K, Song F, Hazelett DJ, Kar SP, Tyrer J, Phelan CM, et al. Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women. Gynecol Oncol. 2019 May;153(2):343–55.
Lawrenson, Kate, et al. “Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.Gynecol Oncol, vol. 153, no. 2, May 2019, pp. 343–55. Pubmed, doi:10.1016/j.ygyno.2019.02.023.
Lawrenson K, Song F, Hazelett DJ, Kar SP, Tyrer J, Phelan CM, Corona RI, Rodríguez-Malavé NI, Seo J-H, Adler E, Coetzee SG, Segato F, Fonseca MAS, Amos CI, Carney ME, Chenevix-Trench G, Choi J, Doherty JA, Jia W, Jin GJ, Kim B-G, Le ND, Lee J, Li L, Lim BK, Adenan NA, Mizuno M, Park B, Pearce CL, Shan K, Shi Y, Shu X-O, Sieh W, Australian Ovarian Cancer Study Group, Thompson PJ, Wilkens LR, Wei Q, Woo YL, Yan L, Karlan BY, Freedman ML, Noushmehr H, Goode EL, Berchuck A, Sellers TA, Teo S-H, Zheng W, Matsuo K, Park S, Chen K, Pharoah PDP, Gayther SA, Goodman MT. Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women. Gynecol Oncol. 2019 May;153(2):343–355.
Journal cover image

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

May 2019

Volume

153

Issue

2

Start / End Page

343 / 355

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Case-Control Studies
  • Carcinoma, Ovarian Epithelial
  • Base Sequence