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


PLoS One. 2013;8(7):e66865


Authors: Zhou B, Song Z, Qian M, Li L, Gong J, Zou S


Abstract

BACKGROUND: CYP2C19 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.

METHODS: To 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.

RESULTS: In 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 (Pā€Š=ā€Š0.006), 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.

CONCLUSIONS: In 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.

PMID: 23874401 [PubMed - in process]