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

• Published in: PloS one Vol. 8; no. 7; p. e66865
• Main Authors: Zhou, Bo, Song, Zhenshun, Qian, Mingping, Li, Liang, Gong, Jian, Zou, Shaowu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.07.2013; Public Library of Science (PLoS)
• Subjects: Aryl Hydrocarbon Hydroxylases - genetics; Asian Continental Ancestry Group; Biology; Breast cancer; Cancer; Cancer genetics; Cancer research; Carcinogens; Colorectal cancer; Confidence intervals; Cytochrome; Cytochrome P-450; Cytochrome P-450 CYP2C19; Cytochrome P450; Digestive system; Digestive System Neoplasms - genetics; Enzymes; Female; Gene mutation; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease - genetics; Genotype; Genotype & phenotype; Health aspects; Health risks; Heterogeneity; Humans; Liver cancer; Male; Mathematics; Medicine; Meta-analysis; Metabolism; Metabolites; Minority & ethnic groups; Mutation; Point mutation; Polymorphism; Polymorphism, Genetic - genetics; Population; Risk; Risk factors; Studies; Surgery; White people
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066865

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. 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. 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 (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. 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.