Functional Polymorphisms in FAS/FASL System Contribute to the Risk of Occurrence but not Progression of Gastric Cardiac Adenocarcinoma

Abstract

Loss of FAS and gain of aberrant FASL expression are common features of malignant transformation. This study was designed to investigate whether the functional polymorphisms of FAS-1377 G/A (rs2234767) and FASL-844 T/C (rs763110) have an effect on the occurrence and progression of gastric cardiac adenocarcinoma (GCA). Associations of the FAS and FASL polymorphisms with GCA were estimated by OR and their 95% confidence intervals using logistic regression. In this study, as compared with the wild type homozygote and heterozygote, either the FAS-1377 AA or FASL-844 CC genotype was associated with increased risk of GCA (OR=1.78; 95% CI, 1.19-2.64 and OR=1.92; 95% CI, 1.46-2.54, respectively). Furthermore, individuals with both the FAS-1377 AA and FASL-844 CC genotypes have a higher risk of GCA (OR=4.09; 95% CI, 2.27-7.37) compared to those with the FAS-1377 GG and FASL-844 TT genotypes. Moreover, the FAS-1377 AA genotype increased the risk of GCA among smokers (OR=1.88; 95% CI, 1.11-3.20) but not among non-smokers, suggesting a potential gene-smoking interaction. This current study suggests that functional polymorphisms in the apoptotic pathway genes FAS and FASL may significantly contribute to the occurrence of GCA.