Poor metabolizers at the cytochrome P450 2C19 loci is at increased risk of developing cancer in Asian populations.

Abstract

CYP2C19 encodes a member of the cytochrome P450 superfamily of enzymes, which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. In the past decade, two common polymorphisms among CYP2C19 (CYP2C19*2 and CYP2C19*3) that are responsible for the poor metabolizers (PMs) phenotype in humans and cancer susceptibility have been investigated extensively; however, these studies have yielded contradictory results.To investigate this inconsistency, we conducted a comprehensive meta-analysis of 11,554 cases and 16,592 controls from 30 case-control studies. Overall, the odds ratio (OR) of cancer was 1.52 [95% confidence interval (CI): 1.23-1.88, P<10(-4)] for CYP2C19 PMs genotypes. However, this significant association vanished when the analyses were restricted to 5 larger studies (no. of cases ≥ 500 cases). In the subgroup analysis for different cancer types, PMs genotypes had an effect of increasing the risks of esophagus cancer, gastric cancer, lung cancer and hepatocellular carcinoma as well as head neck cancer. Significant results were found in Asian populations when stratified by ethnicity; whereas no significant associations were found among Caucasians. Stratified analyses according to source of controls, significant associations were found only in hospital base controls.Our meta-analysis suggests that the CYP2C19 PMs genotypes most likely contributes to cancer susceptibility, particularly in the Asian populations.