Study On NQO1 Polymorphism And Environmental Risk Factors Of Colorectal Cancer Susceptibility

Objectives:To explore the association between genetic polymorphism of NQO1 and susceptibility to colorectal cancer, and the gene-environmental interaction in etiology of colorectal cancer.Methods:A 1:1 matched case-control study with 148 pairs of subjects was carried out in Tianjin People Hospital. Patients with colorectal cancer diagnosed by endoscopical and pathological methods were chosen as cases, while those without the history of malignant tumor were selected as control group who matched to each case according to gender, age and ethnicity. Information was collected through interview using self-designed questionaire, which included demographic data, disease history, behaviors pattern and so on. Polymorphism of NQO1 gene was assessed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Conditional logistic regression was used to analyze the role of environmental factors, gene, gene-environmental interaction in the progress of hepatoma, and to calculate odds ratios (OR) and 95% confidence intervals (CI). Statistic analysis were performed with SPSS Version 16.0.Results:1. The frequencies of three types of NQO1 genotype (CC,CT,TT) in colorectal cancer cases were 27.0%,50.0%,23.0% and 41.9%,42.6%,15.5% in the control group. The distribution in two group was significantly different(χ2=7.751, P=0.021). Compared to NQO1 CC, the patients with CT had a increased risk of colorectal cancer, with OR=1.808(95%CI:1.064-3.072) and those with TT had a higher increased risk of colorectal cancer, OR=2.167(95%CI:1.135-4.136). 2. Results from univariate conditional logistic regression analysis showed that the following factors were significantly associated with the development of CRC: smoke(OR=2.000,95%CI:1.136-3.522), daily quantity of cigarette(OR=1.677, 95%CI:1.162-2.421), years of smoking(OR=396,95%CI:1.080-1.806), the index of smoking(OR=1.636,95%CI:1.150-2.327), stop smoking(OR=1.635,95%CI: 1.131-2.363), daily quantity of wine(OR=1.623,95%CI:1.044-2.523), years of drinking(OR=1.669,95%CI:1.103-2.524), the pickle(OR=1.824,95%CI: 1.285-2.589), the fried food(OR=1.536,95%CI:1.020-2.314), the character of A(OR=1.857,95%CI:1.093-3.157), emotional control(OR=1.440,95%CI:1.021-2.030), interpersonal relationship(OR=1.643,95%CI:1.027-2.628), the history of polyp intestinal(OR=4.400,95%CI:1.666-11.619), family history of cancer(OR=2.364,95%CI:1.168-4.783), education(OR=0.737,95%CI:0.580-0.938), income (OR=0.754,95%CI:0.590-0.965), tea drinking(OR=0.542,95%CI: 0.336-0.873), the years of having tea(OR=0.687,95%CI:0.518-0.910), exercise(OR=0.444,95%CI:0.275-0.719), the years of exercising(OR=0.543,95%CI: 0.383-0.769), hours for of exercise(OR=0.667,95%CI:0.499-0.892), vegetable intake(OR=0.483,95%CI:0.273-0.855), fruit intake(OR=0.510,95%CI: 0.359-0.724), fish intake(OR=0.561,95%CI:0.365-0.864), the milk(OR=0.502, 95%CI:0.308-0.818). The results of multivariate conditional logistic analysis showed that the following factors were significantly associated with CRC:the index of smoking(OR=1.778,95%CI:1.144-2.764), fruit intake(OR=0.495,95%CI: 0.327-0.749), the milk(OR=0.499,95%CI:0.277-0.896), the pickle(OR=1.587, 95%CI:1.046-2.408), the history of polyp intestinal(OR=4.358,95%CI: 1.403-13.543).3. The analysis of gene-environment interaction showed that the multiplicative interaction existed between the following variables:the NQO1 genotype and the index of smoking(OR=1.181,95%CI:1.054-1.324), the NQO1 genotype and the pickle(OR=1.291,95%CI:1.134-1.470).Conclusion:The index of smoking, the pickle, the history of polyp intestinal were the risk factors for colorectal cancer; while fruit and milk were the protective factors of colorectal cancer. This study suggested that NQO1 gene polymorphisms might be associated with the susceptibility to colorectal cancer. There were interaction between the index of smoking, the pickle and genetic polymorphism of NQO1, that would aggravate the risk of colorectal cancer.