Functional polymorphisms in FAS/FASL system contribute to the risk of occurrence but not progression of gastric cardiac adenocarcinoma.

BACKGROUND/AIMS: 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).

METHODOLOGY: Associations of the FAS and FASL polymorphisms with GCA were estimated by OR and their 95% confidence intervals using logistic regression.

RESULTS: 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.

CONCLUSIONS: This current study suggests that functional polymorphisms in the apoptotic pathway genes FAS and FASL may significantly contribute to the occurrence of GCA.