Functional Polymorphisms in the CYP2C19 Gene Contribute to Digestive System Cancer Risk: Evidence from 11,042 Subjects

Abstract

BackgroundCYP2C19 belongs to the cytochrome P450 superfamily of enzymes involved in activating and detoxifying many carcinogens and endogenous compounds, which has attracted considerable attention as a candidate gene for digestive system cancer. CYP2C19 has two main point mutation sites (CYP2C19*2, CYP2C19*3) leading to poor metabolizer (PM) phenotype. In the past decade, the relationship between CYP2C19 polymorphism and digestive system cancer has been reported in various ethnic groups; however, these studies have yielded contradictory results.MethodsTo clarify this inconsistency, we performed this meta-analysis. Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.ResultsIn total, 18 studies with 4,414 cases and 6,628 controls were included. Overall, significantly elevated digestive system cancer risk was associated CYP2C19 PM with OR of 1.66 (95%CI: 1.31–2.10, P<10−5) when all studies were pooled into the meta-analysis. There was strong evidence of heterogeneity (P = 0.006), which largely disappeared after stratification by cancer type. In the stratified analyses according to cancer type, ethnicity, control source and sample size, significantly increased risks were found.ConclusionsIn summary, our meta-analysis suggested that the PM phenotype caused by the variation on CYP2C19 gene is associated with increased risk of digestive system cancer, especially in East Asians.

Quantitative Assessment of Common Genetic Variants on FOXE1 and Differentiated Thyroid Cancer Risk

“…On the other hand, different populations usually have different linkage disequilibrium patterns. A polymorphism may be in close linkage with another nearby causal variant in one ethnic population but not in another [33] . Moreover, it is possible that variation at this locus has modest effects on TC, but environmental factors may predominate in its progress, and mask the effects of this variation.…”

Association between the X-ray repair cross-complementing group 1 Arg194Trp polymorphism and thyroid carcinoma susceptibility: A meta-analysis

“…Second, geographically separated populations tend to demonstrate different linkage disequilibrium patterns. A polymorphism may be in close linkage with another nearby causal polymorphism in one ethnic group, but not in another (Zhou et al, 2013). Third, other confounding factors, such as selection bias and different matching criteria, may also have caused this difference.…”

Pleiotropic Functions of Cytochrome P450 Monooxygenase-Derived Eicosanoids in Cancer

“…In contrast, a decreased breast cancer risk for carriers of the CYP2C19*17 allele was observed in German women (Justenhoven et al, 2009), and a meta-analysis has found that CYP2C19*2 and CYP2C19*17 genotypes are associated with increased survival of breast cancer patients treated with tamoxifen (Bai et al, 2014). Zhou et al found that CYP2C19*2 causes a poor metabolizer phenotype, while CYP2C19*3 is associated with the increased risk of digestive system cancer, especially in East Asians (Zhou et al, 2013). Moreover, poor metabolizer genotypes were found to be associated with the increased risks in many cancers, such as esophagus cancer, gastric cancer, lung cancer, head neck cancer, and hepatocellular carcinoma, suggesting the CYP2C19*2 and CYP2C19*3 most likely contributes to cancer susceptibility, particularly in the Asian populations (Wang et al, 2013).…”