Associations Between GPX1 Pro198Leu Polymorphism and Erythrocyte GPX Activity and Risk of Colorectal Cancer

Abstract

ISEE-476 Objective: GPX1 encodes the enzyme glutathione peroxidase 1 (GPX1), which may counteract oxidative DNA damage caused by reactive oxygen species from environmental and lifestyle sources. We examined prospectively whether the GPX1 Pro198Leu polymorphism or low enzyme activity in erythrocytes increases the risk of colorectal cancer, and assessed the interactions between the polymorphism/enzyme activity and dietary components or smoking in risk of colorectal cancer. Material and Methods: We identified 375 cases and selected a comparison group of 779 individuals matched on gender, all nested in the prospective “Diet, Cancer and Health” study of 57,053 Danes. Genotype was determined by endpoint reading on a Sequence Detection system ABI 7500. GPX enzyme activity was measured on a Roche/Hitachi 912 analyzer. Information on dietary components and smoking was obtained from questionnaires filled in at enrolment in 1993 to 1997. Results: We found no association between the GPX1 polymorphism and colorectal cancer, but observed statistically significant interaction (P = 0.01) between the polymorphism and alcohol consumption with an incidence rate ratio (IRR) of colorectal cancer of 1.47 (95% CI: 1.17–1.84) per 10 g alcohol intake per day among homozygous 198Leu carriers. Among these subjects IRR was 1.67 (CI: 1.06–2.65) per 10 g tobacco per day (P = 0.06). We found correlation between the GPX1 polymorphism and enzyme activity (P = 0.05). GPX activity was not associated with colorectal cancer. The activity was negatively correlated with smoking intensity (r = −0.12, P < 0.0001) and positively correlated with intake of fruits and vegetables (r = 0.09, P = 0.0012). No association was observed between GPX activity and alcohol consumption. Conclusions: Interaction was observed between alcohol consumption and the GPX1 Pro198Leu polymorphism in relation to colorectal cancer, which suggests that an adverse association between alcohol and colorectal cancer may be strongest among homozygous 198Leu carriers. GPX activity correlated with the polymorphism. Smoking intensity and intake of fruit and vegetables were predictors for GPX activity.