Allelic polymorphism of GSTM1 and NAT2 genes modifies dietary-induced DNA damage in colorectal mucosa

Typically, cancer is caused by the interaction of genetic and environmental factors. In colorectal carcinogenesis, diet and nutritional habits are the most important external risk determinants. Allelic polymorphisms of certai n metabolizing enzymes may have an influence on cancer risk by modifying th e concentration of active carcinogenic compounds in the body. In the presen t study we investigated the interaction between nutritional and genetic sus ceptibility factors in human colon carcinogenesis. Healthy volunteers were divided into four groups, based on allelic polymorphisms of N-acetyltransfe rase 2 and glutathione-S-transferase M1 enzymes. Comet assay was used to de termine the level of DNA strand breaks in exfoliated colorectal mucosal cel ls, following a 2-day vegetarian diet, and after switching to a 2-day 'high -meat' diet. The 'high-meat' diet statistically significantly increased the amount of single-strand breaks in rapid acetylators and among individuals with a GSMT1 + genotype, while it caused only a slight and not significant increase in the other groups. Our study emphasizes the importance of using susceptibility markers in cancer epidemiology, since environmental effects are strongly modified by these genetic factors. (C) 2000 Lippincott William s & Wilkins.