Quantitative assessment of the influence of cytochrome P450 2C19 gene polymorphisms and digestive tract cancer risk

Abstract

Cytochrome P450 (CYP) 2C19 metabolizes many promutagens and procarcinogens to biologically active metabolites, which strongly promote proliferation of cancer cells in vitro and in vivo. The CYP2C19 gene exhibits several genetic polymorphisms that are thought to play a major role in inter-individual variability in drug response, drug-xenobiotic interactions, and in cancer susceptibility. Two polymorphisms of the CYP2C19 gene (CYP2C19*2, CYP2C19*3) which was associated with reduced enzyme activity have been investigated extensively digestive tract cancer; however, these studies have yielded contradictory results. To clarify this inconsistency, we performed this meta-analysis including 15 case-control studies with a total of 3,252 cases and 6,269 controls. Overall, we found significant association between CYP2C19*2 and digestive tract cancer (OR = 1.27, 95 % CI, 1.07-1.51, P = 0.007) while no significant results were found for CYP2C19*3. Potential sources of heterogeneity including cancer types, ethnicity, source of control, and sample size of study were assessed. In the subgroup analyses by cancer types, significant association was detected only in esophagus cancer for CYP2C19*2. When stratified by ethnicity, significantly increased risks were found for the CYP2C19*2 polymorphism among Asians. This meta-analysis demonstrated that the CYP2C19*2 polymorphism is a risk factor for developing digestive tract cancer. However, additional very large-scale studies are warranted to provide conclusive evidence on the effects of the CYP2C19 gene on risk of digestive tract cancer.