Browsing by Author "Phelan, Catherine M"
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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 Restricted Risk of ovarian cancer and inherited variants in relapse-associated genes.(PLoS One, 2010-01-27) Peedicayil, Abraham; Vierkant, Robert A; Hartmann, Lynn C; Fridley, Brooke L; Fredericksen, Zachary S; White, Kristin L; Elliott, Elaine A; Phelan, Catherine M; Tsai, Ya-Yu; Berchuck, Andrew; Iversen, Edwin S; Couch, Fergus J; Peethamabaran, Prema; Larson, Melissa C; Kalli, Kimberly R; Kosel, Matthew L; Shridhar, Vijayalakshmi; Rider, David N; Liebow, Mark; Cunningham, Julie M; Schildkraut, Joellen M; Sellers, Thomas A; Goode, Ellen LBACKGROUND: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk. METHODS AND FINDINGS: Women with and without invasive ovarian cancer (749 cases, 1,041 controls) were genotyped at 136 single nucleotide polymorphisms (SNPs) within 13 candidate genes. Risk was estimated for each SNP and for overall variation within each gene. At the gene-level, variation within MSL1 (male-specific lethal-1 homolog) was associated with risk of serous cancer (p = 0.03); haplotypes within PRPF31 (PRP31 pre-mRNA processing factor 31 homolog) were associated with risk of invasive disease (p = 0.03). MSL1 rs7211770 was associated with decreased risk of serous disease (OR 0.81, 95% CI 0.66-0.98; p = 0.03). SNPs in MFSD7, BTN3A3, ZNF200, PTPRS, and CCND1A were inversely associated with risk (p<0.05), and there was increased risk at HEXIM1 rs1053578 (p = 0.04, OR 1.40, 95% CI 1.02-1.91). CONCLUSIONS: Tumor studies can reveal novel genes worthy of follow-up for cancer susceptibility. Here, we found that inherited markers in the gene encoding MSL1, part of a complex that modifies the histone H4, may decrease risk of invasive serous ovarian cancer.