Dietary intake of heterocyclic amines, meat-derived mutagenic activity, and risk of colorectal adenomas

Meats cooked well-done by high temperature techniques produce mutagenic com pounds such as heterocyclic amines (HCAs), but the amounts of these compoun ds vary by cooking techniques, temperature, time, and type of meat. We inve stigated the role of KCAs in the etiology of colorectal adenomas and the ex tent to which they may explain the previously observed risk for red meat an d meat cooking methods. In a case-control study of colorectal adenomas, cas es (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or co lonoscopy, and controls (n = 228) were found not to have colorectal adenoma s at sigmoidoscopy. Using a meat-derived HCA and mutagen database and respo nses from a meat-cooking questionnaire module, we estimated intake of 2-ami no-3,4,8-trimethylimidazo[45-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethyli midazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]p (PhIP) and mutagenic activity. We calculated odds ratios and 95% confidence intervals using logistic regression adjusting for several established risk factors for colorectal adenomas or cancer. The odds ratios (95% confidence interval; P for trend test) fifth versus first quintiles are: 2.2 (1.2-4.1 ; P = 0.02) for DiMeIQx; 2.1 (1.0-4.3; P = 0.002) for MeIQx; 2.5(1.1-5.5; P = 0.02) for PhIP; and 3.1 (1.4-6.8; P = 0.001) for mutagenic activity. Whe n the three HCAs were adjusted for the other two, only the trend for MeIQx (P = 0.04) remained statistically significant, When we tried to disentangle the relative contribution of the three HCAs from the meat variables, we fo und that MeIQx: even when adjusted for red meat but not vice versa. When Me IQx and well-done meat were analyzed in the same model, the risks were atte nuated for both. Mutagenic activity from meat remained significantly associ ated with increased risk even when adjusted for intake of red meat or well- done red meat, whereas the red meat and well-done red meat associations wer e no longer significant when adjusted for total mutagenic activity, In conc lusion, we found an elevated risk of colorectal adenomas associated with hi gh intake of certain HCAs, Further, mutagenic activity from cooked meat con sumption, a measure that integrates all of the classes of mutagens, was str ongly associated with risk and explained the excess risk with intake of wel l done red meat.