genetic variants in tgf-β pathway are associated with ovarian cancer risk基因变异在tgf-β通路与卵巢癌风险相关联.pdfVIP
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genetic variants in tgf-β pathway are associated with ovarian cancer risk基因变异在tgf-β通路与卵巢癌风险相关联
Genetic Variants in TGF-b Pathway Are Associated with Ovarian Cancer Risk 1 2 1 3 1 1 2 Jikai Yin , Karen Lu , Jie Lin , Lei Wu , Michelle A. T. Hildebrandt , David W. Chang , Larissa Meyer , 1 4 Xifeng Wu , Dong Liang * 1 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 2 Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 3 Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, Texas, United States of America, 4 College of Pharmacy, Texas Southern University, Houston, Texas, United States of America Abstract The transforming growth factor- b (TGF-b) signaling pathway is involved in a diverse array of cellular processes responsible for tumorigenesis. In this case-control study, we applied a pathway-based approach to evaluate single-nucleotide polymorphisms (SNPs) in the TGF-b signaling pathway as predictors of ovarian cancer risk. We systematically genotyped 218 SNPs from 21 genes in the TGF-b signaling pathway in 417 ovarian cancer cases and 417 matched control subjects. We analyzed the associations of these SNPs with ovarian cancer risk, performed haplotype analysis and identified potential cumulative effects of genetic variants. We also performed analysis to identify higher-order gene-gene interactions influencing ovarian cancer risk. Individual SNP analysis showed that the most significant SNP was SMAD6: rs4147407, with an adjusted odds ratio (OR) of 1.60 (95% confidence interval [CI], 1.14–2.24, P = 0.0066). Cumulative genotype analysis of 13
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