Exposure to heterocyclic aromatic
amines (HAAs),
carcinogens produced when meat is cooked at high temperatures, is an emerging risk factor for
colorectal cancer (CRC). In a cross-sectional study of 342 patients undergoing a screening colonoscopy, the role of 2-amino-1-methyl-6-phenylimidazo[4,5-
b]pyridine (
PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]
quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]
quinoxaline (DiMeIQx), the three most abundant HAAs found in cooked meats, and total mutagenic activity in cooked meats were examined in relation to colorectal
adenoma risk. Given that genetic differences in the ability to biotransform HAAs and repair
DNA are postulated to modify the HAA-CRC relationship, gene-diet interactions were also examined. Among the total study population, no relationships were observed between dietary HAAs or meat mutagenicity, and colorectal
adenoma risk; however, in males, positive associations between dietary HAAs/meat mutagenicity exposures and
adenoma risk were suggestive of a relationship. In a separate analysis, polymorphisms in CYP1B1 were found to be associated with colorectal
adenoma risk. Additionally, gene-diet interactions were observed for dietary
PhIP and polymorphisms in CYP1B1 and XPD, dietary DiMeIQx and XPD polymorphisms, and meat mutagenicity exposure and CYP1B1 polymorphisms. Overall, increased colorectal
adenoma risk was observed with higher HAA/meat mutagenicity exposures among those with polymorphisms which confer greater activity to biotransform HAAs and/or lower ability to repair
DNA. This research supports the link between dietary HAAs and
genetic susceptibility in colorectal
adenoma etiology. The vast majority of
CRCs arise from colorectal
adenomas; thus, the results of this study suggest that changes in meat preparation practices limiting the production of HAAs may be beneficial for CRC prevention.