Browsing by Author "Goodman, Marc T"
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Item Open Access Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.(Gynecologic oncology, 2019-03-19) Lawrenson, Kate; Song, Fengju; Hazelett, Dennis J; Kar, Siddhartha P; Tyrer, Jonathan; Phelan, Catherine M; Corona, Rosario I; Rodríguez-Malavé, Norma I; Seo, Ji-Hei; Adler, Emily; Coetzee, Simon G; Segato, Felipe; Fonseca, Marcos AS; Amos, Christopher I; Carney, Michael E; Chenevix-Trench, Georgia; Choi, Jiyeob; Doherty, Jennifer A; Jia, Weihua; Jin, Gang J; Kim, Byoung-Gie; Le, Nhu D; Lee, Juyeon; Li, Lian; Lim, Boon K; Adenan, Noor A; Mizuno, Mika; Park, Boyoung; Pearce, Celeste L; Shan, Kang; Shi, Yongyong; Shu, Xiao-Ou; Sieh, Weiva; Australian Ovarian Cancer Study Group; Thompson, Pamela J; Wilkens, Lynne R; Wei, Qingyi; Woo, Yin L; Yan, Li; Karlan, Beth Y; Freedman, Matthew L; Noushmehr, Houtan; Goode, Ellen L; Berchuck, Andrew; Sellers, Thomas A; Teo, Soo-Hwang; Zheng, Wei; Matsuo, Keitaro; Park, Sue; Chen, Kexin; Pharoah, Paul DP; Gayther, Simon A; Goodman, Marc TOBJECTIVE: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.Item Open Access Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.(Am J Epidemiol, 2016-10-15) Clyde, Merlise A; Palmieri Weber, Rachel; Iversen, Edwin S; Poole, Elizabeth M; Doherty, Jennifer A; Goodman, Marc T; Ness, Roberta B; Risch, Harvey A; Rossing, Mary Anne; Terry, Kathryn L; Wentzensen, Nicolas; Whittemore, Alice S; Anton-Culver, Hoda; Bandera, Elisa V; Berchuck, Andrew; Carney, Michael E; Cramer, Daniel W; Cunningham, Julie M; Cushing-Haugen, Kara L; Edwards, Robert P; Fridley, Brooke L; Goode, Ellen L; Lurie, Galina; McGuire, Valerie; Modugno, Francesmary; Moysich, Kirsten B; Olson, Sara H; Pearce, Celeste Leigh; Pike, Malcolm C; Rothstein, Joseph H; Sellers, Thomas A; Sieh, Weiva; Stram, Daniel; Thompson, Pamela J; Vierkant, Robert A; Wicklund, Kristine G; Wu, Anna H; Ziogas, Argyrios; Tworoger, Shelley S; Schildkraut, Joellen MPreviously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010). We developed a hierarchical logistic regression model for predicting case-control status that included imputation of missing data. We randomly divided the data into an 80% training sample and used the remaining 20% for model evaluation. The AUC for the full model was 0.664. A reduced model without SNPs performed similarly (AUC = 0.649). Both models performed better than a baseline model that included age and study site only (AUC = 0.563). The best predictive power was obtained in the full model among women younger than 50 years of age (AUC = 0.714); however, the addition of SNPs increased the AUC the most for women older than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to estimate absolute risk and evaluating it in prospective data sets is warranted.