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.
Wang
Jaw-Yuan
JY
Cancer Center, and Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yang
I-Ping
IP
Wu
Deng-Chyang
DC
Huang
Szu-Wei
SW
Wu
Jeng-Yih
JY
Juo
Suh-Hang Hank
SH
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D013624:Taiwan
C486484:GPX3 protein, human; D005979:Glutathione Peroxidase