Role Of Alcohol-metabolizing Enzymes Gene Polymorphisms And Environmental Exposure On Risk And Progression Of Colorectal Cancer: A Molecular Epidemiology Study

Objective:To explore the interactions of gene polymorphisms of Alcohol dehydrogenase1B (ADH1B)(rs1229984), Aldehyde dehydrogenase2(ALDH2)(rs671), CytochromeP4502E1(CYP2E1)(rs1329149) with risk environmental exposures and theinteractions between gene-gene in the colorectal cancer(CRC) and the roles ofgenotypes and environmental exposures in the development of colorectal cancer.Method:With a case-only study, a total of472participants were enrolled between2007and2009in this study. Data on demographic characteristic, history of environmentalexposure and clinicopathological parameters were obtained from all participantsthrough a written questionnaire. Genotypes were determined by SequenomMassARRAY system. Unconditional logistic regression analysis was employed toinvestigate statistical interactions between environmental exposures and genepolymorphisms and between the three genes in dominant model and recessive modelin all participants. The stratified analyses were also performed to explore thegene-environmental and gene-gene interactions according to cancer location whichwere defined by colon cancer and rectal cancer. The χ2test and unconditional logisticregression were used to assess the associations between genotypes and environmentalexposures and the metastasis risk of CRC.Results:1、There was a significant multiplicative interaction for CRC risk betweencarriership of at least one of the ADH1B(rs1229984)(G) allele and overweight(OR=1.720,95%CI=1.038-2.848, P=0.0352; ORadj=1.785,95%CI=1.061-3.002,P=0.0290）。2、There was no significant interaction for CRC risk between smoking andADH1B(rs1229984) under adjusted sex age and drinking（OR=0.597,95%CI=0.387～0.921, P=0.0196; ORadj=0.922,95%CI=0.509-1.669, P=0.7882）；3、In stratified analyses, a significant multiplicative interaction for rectal cancer risk between carriership of at least one of the ADH1B(rs1229984)(G) allele andoverweight was found（OR=2.209,95%CI=1.084-3.796, P=0.0268; ORadj=1.960,95%CI=1.025-3.748, P=0.0419）.4、The correlations between genotypes and environmental exposures and Dukesstage were not significant.Conclusion:The observed significant positive gene-environmental interactions suggested thatthe risk increased for CRC conferred by BMI and ADH1B (rs1229984). Our findingswarrant further investigation in epidemiological and functional studies to elucidatepathophysiology as well as to aid in the development of recommendations for diseaseprevention.