Meta-analysis of Association Studies of CYP1A1 Genetic Polymorphisms with Digestive Tract Cancers Susceptibility in Chinese


Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) geneticpolymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, includingesophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but theresults are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and
Methods:Eligible case-control studies published until December 2013 were retrieved by systematic literature searches fromPubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associatedliterature was acquired through deliberate search and selection based on established inclusion criteria. Fixedeffectsor random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis wasconducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified andsensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability andstability.
Results: Eighteen cases control studies with 1, 747 cases and 2, 923 controls were selected for CYP1A1MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancerssusceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52-2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [ GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestivetract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val geneticpolymorphisms with EC in China. However, available data collected by the study failed to reveal remarkableassociations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspIgenetic polymorphisms.
Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, butnot CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinesepopulations. Additional well-designed studies, with larger sample size, focusing on different ethnicities andcancer types are now warranted to validate this finding.