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• W2005163988 abstract "Objectives : Observational studies and intervention trials suggest that selenium has potential cancer prevention properties. We previously found that selenium supplementation reduces cancer mortality, particularly gastric cancer mortality, in a high-risk region in China, and that low serum selenium concentration is associated with increased risks of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). In humans, selenium may exert chemopreventive actions through the 25 known selenoproteins, which contain residues of selenocysteine, the 21st amino acid. Therefore, genetic variants in selenoprotein genes may influence susceptibility to ESCC and GCA, yet no previous studies have comprehensively investigated these potential associations. Thus, we examined the association between genetic variants in selenoprotein and selenium metabolism genes and risks of ESCC and GCA. Methods : We included 1027 ESCC and 753 GCA cases plus 1452 controls from two epidemiologic studies in the high-risk region in China. We genotyped 272 tag single nucleotide polymorphisms (SNPs) in all 25 known selenoprotein genes and 4 selenium metabolism genes. For each gene, we calculated a standardized summary p-value using the adaptive rank truncated product (ARTP) method. For SNPs, logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results : In gene-based tests, the selenoprotein gene SELS (selenoprotein S) was associated with ESCC risk (p=0.00070); TXNRD2 (thioredoxin reductase 2) showed borderline non-significant associations with both ESCC (p=0.063) and GCA (p=0.051). In SNP-based tests for these two genes, rs8029790 (tagged to SELS in the upstream noncoding region) was associated with a 1.30-fold increased risk of ESCC (CI=1.14, 1.47; p=0.000052), whereas rs2073750 (tagged to intron in TXNRD2) was associated with risks of both ESCC (OR=0.84, CI=0.74, 0.94; p=0.0029) and GCA (OR=0.82, CI=0.72, 0.93; p=0.0026). Conclusions : The potential anticarcinogenic properties of selenium may be due to its presence as the amino acid selenocysteine in human selenoproteins. The association of SNPs in selenoprotein genes SELS and TXNRD2 with ESCC and GCA risk suggests that selenium and these selenoproteins may play an important role in cancer development. Our findings warrant further research on elucidating the functional effects of these SNPs on selenoproteins in the context of upper gastrointestinal (UGI) carcinogenesis so that we can better understand the role of selenium supplementation in cancer prevention. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A59." @default.
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• W2005163988 date "2011-10-01" @default.
• W2005163988 modified "2023-09-30" @default.
• W2005163988 title "Abstract A59: Selenoprotein gene variants and risk of esophageal and gastric cancer in a Chinese population" @default.
• W2005163988 doi "https://doi.org/10.1158/1940-6207.prev-11-a59" @default.
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