Abstract
Abstract PURPOSE: Several observational studies and multinutrient interventional trials suggest that selenium compounds have potential chemopreventive effects on esophageal and gastric carcinogenesis, presumably via their influence on selenoproteins. We aimed to investigate associations between genetic variants in selenoprotein genes and risk of esophageal squamous cell carcinoma (ESCC), gastric carcinoma (GC) and GC subsets: cardia (GCA) and non-cardia (GNCA) using data from a genome-wide association study in a Han Chinese population in which ESCC and GC are predominant cancers. METHODS: 1944 ESCC cases, 1758 GC cases (1126 GCA and 632 GNCA) and 2111 controls from the Shanxi Upper GI Cancer Genetics project and the Linxian Nutritional Intervential Trials were genotyped for 243 SNPs in 24 selenoprotein genes. Logistic regression models were applied to evaluate SNP-level associations. Pathway- and gene-level associations were determined using the resampling-based adaptive rank-truncated product approach. RESULTS: Selenoproteins as a whole pathway were not significantly associated with ESCC (p=0.398) or GC (p=0.608), but five significant (p<0.05) gene-level associations were identified, including GPX2 (p=0.008) and GPX5 (p=0.006) with ESCC, DIO2 (p=0.026) with GC, and SEPP1 (p=0.007) and SEPW1 (p=0.004) with GCA. CONCLUSION: Our results show evidence for an association between specific selenoprotein genes and the risk of ESCC and GC, warranting further studies to validate these associations and investigate underlying mechanisms. Citation Format: Sharon Li, Paula L. Hyland, Neal D. Freedman, Nan Hu, Hua Su, Lemin Wang, Chaoyu Wang, Ti Ding, Yuan Wang, Jin-Hu Fan, You-Lin Qiao, Xiaoqin Xiong, Kai Yu, Alisa M. Goldstein, Sanford M. Dawsey, Philip R. Taylor, Christian C. Abnet, Shih-Wen Lin. Genetic variants in selenoprotein genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2206. doi:10.1158/1538-7445.AM2014-2206
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