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Functional polymorphisms in the CYP2C19 gene contribute to digestive system cancer risk: evidence from 11,042 subjects.

ABSTRACT: 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.

SUBMITTER: Zhou B

PROVIDER: S-EPMC3712993 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Functional polymorphisms in the CYP2C19 gene contribute to digestive system cancer risk: evidence from 11,042 subjects.

Zhou Bo B Song Zhenshun Z Qian Mingping M Li Liang L Gong Jian J Zou Shaowu S

PloS one 20130716 7

<h4>Background</h4>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 ...[more]

PMID: 23874401

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Project description:Background and objectivesDiets containing red or processed meat are associated with a growing risk of digestive system cancers. Whether a plant-based diet is protective against cancer needs a high level of statistical evidence.MethodsWe performed a meta-analysis of five English databases, including PubMed, Medline, Embase, Web of Science databases, and Scopus, on October 24, 2021 to identify published papers. Cohort studies or case-control studies that reported a relationship between plant-based diets and cancers of the digestive system were included. Summary effect-size estimates are expressed as Risk ratios (RRs) or Odds ratios (ORs) with 95% confidence intervals and were evaluated using random-effect models. The inconsistency index (I2) and τ2 (Tau2) index were used to quantify the magnitude of heterogeneity derived from the random-effects Mantel-Haenszel model.ResultsThe same results were found in cohort (adjusted RR = 0.82, 95% CI: 0.78-0.86, P < 0.001, I 2 = 46.4%, Tau2 = 0.017) and case-control (adjusted OR = 0.70, 95% CI: 0.64-0.77, P < 0.001, I 2 = 83.8%, Tau2 = 0.160) studies. The overall analysis concluded that plant-based diets played a protective role in the risk of digestive system neoplasms. Subgroup analyses demonstrated that the plant-based diets reduced the risk of cancers, especially pancreatic (adjusted RR = 0.71, 95% CI: 0.59-0.86, P < 0.001, I 2 = 55.1%, Tau2 = 0.028), colorectal (adjusted RR = 0.76, 95% CI: 0.69-0.83, P < 0.001, I 2 = 53.4%, Tau2 = 0.023), rectal (adjusted RR = 0.84, 95% CI: 0.78-0.91, P < 0.001, I 2 = 1.6%, Tau2 = 0.005) and colon (adjusted RR = 0.88, 95% CI: 0.82-0.95, P < 0.001, I 2 = 0.0%, Tau2 = 0.000) cancers, in cohort studies. The correlation between vegan and other plant-based diets was compared using Z-tests, and the results showed no difference.ConclusionsPlant-based diets were protective against cancers of the digestive system, with no significant differences between different types of cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322276, Identifier: CRD42022322276.

Dataset Information

Functional polymorphisms in the CYP2C19 gene contribute to digestive system cancer risk: evidence from 11,042 subjects.

Publications

Functional polymorphisms in the CYP2C19 gene contribute to digestive system cancer risk: evidence from 11,042 subjects.

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