The Relation Between Genetic Polymorphism Of Quinone Oxidore-ductase1(NQO1),N-acetyltransferase2 (NAT2) And Susceptibility To Colorectal Cancer

ObjectiveThe study intended to investigate the association between genetic polymorphism of NQO1,NAT2 and susceptibility to Colorectal Cancer, and the gene-environmental interaction in etiology of Colorectal Cancer. Materials & methodsUsing 1:1 matched case-control study, we have identified 286 Colorectal Cancer patients with endoscopy and pathology diagnosis from big hospitals during the periods in Fuzhou city. A total of 286 controls without history of malignant tumor were selected during the same period and matched to each case by gender, age, nationality and inhabited areas.The constructed questionnaires were administered, and the geneotyping of NQO1,NAT2 was examined with PCR-RFLP analysis.Conditional logistic regression was used to analyze the role of environmental factors, gene, gene-environmental in the progress of hepatoma, and to calculate odds ratios and 95% confidence intervals. All the calculations and statistics were performed with the computer program, SPSS Version 11.5.Results1.Multivariate conditional logistic regression analysis showed that well water, fountain, stodge, the family history of cancer,intestinal tract diseases ,tobacco smoking amount each day; while coarse grains was the protective factor of colorectal cancer.2.The frequencies NQO1 c/c,c/t and t/t genotype in colorectal cance cases were 23.77%,52.10%,24.13% and c/c,c/t and t/t genotype in the control group were 40.56%,44.06%,15.38%. The distribution in two group was significant difference (χ2=12.397,P =0.002).Compared to wild-type homozygote , NQO1 heterozygote had a increased risk of colorectal cancer, OR=2.061(95%CI :1.372～3.097).Mutant homozygote had a increased risk of colorectal, OR=2.640 (95%CI :1.568～4.444).3.The frequencies NAT2 genotype in colorectal cance cases were 38.81%,3.50 %,18.18%,19.93%,19.58% and the genotype in the control group were 58.39 %,3.85%,13.29%,14.33%,10.14%. The distribution in two group was significant difference (χ2 = 24.695 , P <0.001).Compared to wild-type homozygote (wt/wt), NAT2 wt/m1 had a increased risk of colorectal cancer, OR=2.004(95%CI :0.737～5.450), NAT2 wt/m2 had a increased risk of colorectal cancer, OR= 2.210(95%CI :1.288～3.793),NAT2 wt/m3 had a increased risk of colorectal cancer, OR= 2.280(95%CI :1.355～3.836),NAT2 mx/mx had a increased risk of colorectal cancer, OR=3.145(95%CI :1.812～5.456).Compared to rapid type genotype , NAT2 slow type had a increased risk of colorectal cancer, OR=2.155(95%CI :1.312～3.541) .4. The analysis of gene-environment interaction showed that tobacco smoking amount appeared interaction with genetic polymorphism of NQO1, P interaction =5.308,P=0.004. ConclusionWell water, fountain, stodge, the family history of cancer,intestinal tract diseases ,tobacco smoking amount each day were the risk factors for colorectal cancer; while coarse grains was the protective factor of colorectal cancer. This study suggested that NQO1,NAT2 gene polymorphisms might be associated with the susceptibility to colorectal cancer. There was interaction between tobacco smoking amount and genetic polymorphism of NQO1,that would aggravate the risk of suffering from colorectal cancer.