A recent report issued jointly by the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) concluded that the evidence to support a positive association between greater intakes of red and processed meat and colorectal cancer was convincing, but the evidence for specific meat components explaining these associations remained inconclusive. To explore potential underlying mechanisms for these observations, we examined associations of mutagens generated through meat cooking and meat processing methods with colorectal cancer in a large multisite population-based case-control study in a contiguous 19-county area in central and northeast Pennsylvania. Participants (863 healthy controls, 483 incident colon and 196 incident rectal cancer cases) completed a detailed lifestyle questionnaire and the 137-item National Cancer Institute's Diet History Questionnaire (DHQ). The DHQ included a detailed cooked and processed meat module to estimate intakes of heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), nitrites, and nitrates. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between meat exposures and colorectal cancer stratified by sub-site of the large intestine were estimated from unconditional logistic regression models. After multivariate adjustment for age, total energy intake, sex, body mass index, energy-adjusted total fruit and vegetable intake, and past regular NSAID use, positive associations with HCAs and PAHs, as measured by total mutagenic activity, were stronger for rectal cancer (OR = 1.55, 95% CI: 0.97, 2.47; P for trend = 0.049) than colon cancer, whereas positive associations with nitrites plus nitrates were stronger for colon cancer (OR = 1.31, 95% CI: 0.91-1.87; P for trend = 0.031). Our findings support the hypothesis that greater exposure to HCAs, PAHs, nitrites, and nitrates is a plausible mechanism by which red and processed meat may increase colorectal cancer risk. Our sub-site analyses indicate that associations between meat-derived exposures and colon and rectal cancer may differ, which underscores the need for additional studies that examine dietary risk factors for colon and rectal cancer as separate endpoints. The investigation of interactions between genetic polymorphisms and meat exposures in relation to colorectal cancer risk is underway in our study population.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):A84.