Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer

Background: Glutathione peroxidase 3 (GPX3) can enhance an antioxidant's capacity and reduce genomic damage caused by oxidants and thus influence tumorigenesis. We investigated the role of GPX3 as a risk of gastric cancer. Methods: We first conducted a case-control study to test for the association between 5 tagging single nucleotide polymorphisms (SNPs) of GPX3 and the risk of gastric cancer in Chinese. Multivariate logistic regression analysis was performed to estimate the genetic effect with adjustments for age and sex. Functional studies were performed by using the luciferase reporter assay to assess functional consequences of the significant SNPs. Results: Among five SNPs (rs3763013, rs8177412, rs3805435, rs3828599, and rs2070593) genotyped in 227 cases and 844 controls. 3 SNPs were significant: intronic SNP rs3805435 (OR = 0.70, P = 0.037). intronic SNP 3828599 (OR = 0.68, P= 0.025), and 3' UTR SNP rs2070593 (OR = 0.48, P = 0.001). The two intronic SNPs rs3805435 and SNP rs3828599 were in linkage disequilibrium (D' = 0.91). Conclusions: The reporter assays showed significant difference in the luciferase expression between protective and risk alleles of 2o intronic SNPs (P = 0.004), whereas the 3'UTR SNP did not influence the luciferase expression. The intronic SNPs at GPX3 can influence gene expression leading to an alteration of gastric cancer risk (C) 2010 Elsevier B.V. All rights reserved.