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.
Highlights
Cytochrome P450 2C19 (CYP2C19), one of the isoforms of CYP enzymes, is a clinically important enzyme responsible for the metabolism of a number of therapeutic drugs, such as clopidogrel, omeprazole, lansoprazole, rabeprazole, diazepam, propranolol and S-mephenytoin [1,2,3,4,5,6]
Literature search strategy Epidemiological association studies published before the end of December, 2012, on digestive system cancer and CYP2C19 were sought by computer-based searches from databases including MEDLINE, PubMed, EMBASE, ISI web of science and CNKI (China National Knowledge Infrastructure) without language restriction
Search term combinations were keywords relating to the gene (‘‘Cytochrome P450 2C19 or CYP2C19’’), in combination with words related to cancer (‘‘cancer, carcinoma, tumor or neoplasm’’), and ‘‘polymorphism or variant’’
Summary
Cytochrome P450 2C19 (CYP2C19), one of the isoforms of CYP enzymes, is a clinically important enzyme responsible for the metabolism of a number of therapeutic drugs, such as clopidogrel, omeprazole, lansoprazole, rabeprazole, diazepam, propranolol and S-mephenytoin [1,2,3,4,5,6]. The nucleotide changes in the CYP2C19*2 and *3, lead to a splicing defect and stop codon, respectively, and to nonfunctional proteins, the name poor metabolizer (PM) phenotype [12]. They represent more than 99% of all the abnormal CYP2C19 alleles in Asian population and 87% in Caucasian population. The wild type CYP2C19*1 gene is categorized as extensive metabolizer (EM) phenotype. 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. The relationship between CYP2C19 polymorphism and digestive system cancer has been reported in various ethnic groups; these studies have yielded contradictory results
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