Abstract

BackgroundGenetic polymorphism (rs762551A>C) in gene encoding cytochrome P450 1A2 (CYP1A2) has been shown to influence the inducibility of CYP1A2 expression and thus might be associated with risk of several types of human cancer. However, the results of previous studies on the associations of this polymorphism with risk of cancer are not all consistent. To clarify the potential contribution of CYP1A2 rs762551 to cancer risk, we performed a meta-analysis of the published case–control studies.MethodsWe used PubMed, Embase, OVID, ScienceDirect, and Chinese National Knowledge Infrastructure databases to identify the related publications for this meta-analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random effect model to evaluate the association of rs762551 with cancer risk. A χ2-based Q-test was used to examine the heterogeneity assumption and the funnel plot and Egger’s test were used to examine the potential publication bias. The leave-one-out sensitivity analysis was conducted to determine whether our assumptions or decisions have a major effect on the results of the review.ResultsOur analysis of 19 eligible case–control studies showed a significant association between rs762551C variant with risk of cancer in the genetic model of CC versus AA (OR = 1.30, 95% CI = 1.02-1.64) and the dominant model (OR = 1.19, 95% CI = 1.04-1.36). In subgroup analysis based on ethnicity, the rs762551CC genotype was associated with increased cancer risk (OR = 1.29, 95% CI = 1.27-1.63 in co-dominate model and OR = 1.17, 95% CI = 1.02-1.34 in dominant model in Caucasians, but not in Asians and the mixed population.ConclusionThese results suggested that CYP1A2 rs762551 polymorphism is likely to be associated with susceptibility to cancer in Caucasians.

Highlights

  • Genetic polymorphism in gene encoding cytochrome P450 1A2 (CYP1A2) has been shown to influence the inducibility of CYP1A2 expression and might be associated with risk of several types of human cancer

  • Methods for quantitative analysis We examined the association between CYP1A2 rs762551 A>C polymorphism and the risk of cancer by calculating pooled odds ratio (ORs) and 95% confidence intervals (CI) in genetic model of CC versus AA, dominant model (CC+CA versus AA) and recessive model (CC versus CA+AA)

  • The genotyping frequencies of CYP1A2 rs762551 polymorphism were in agreement with the Hardy-Weinberg equilibrium in both cases and controls

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Summary

Introduction

Genetic polymorphism (rs762551A>C) in gene encoding cytochrome P450 1A2 (CYP1A2) has been shown to influence the inducibility of CYP1A2 expression and might be associated with risk of several types of human cancer. The results of previous studies on the associations of this polymorphism with risk of cancer are not all consistent. There have several reported studied three common variations, that is -3860G>A polymorphism (CYP1A2*1C; rs2069514) [8,9], -739G>T polymorphism (rs2069526) [8,10] and 1545T>C polymorphism (rs2470890) [10,11] These polymorphisms may be related to altered inducibility of CYP1A2 expression by environmental chemicals and influence the individual susceptibility to certain cancer. The CYP1A2 rs2069514 A allele has been demonstrated to associated with decreased enzyme activity in smokers and CYP1A2 rs762551 polymorphism is associated with altered expression of CYP1A2 by cigarette smoking [12,13,14]

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