Meat‐related mutagens/carcinogens in the etiology of colorectal cancer

Abstract

Diets containing substantial amounts of red or preserved meats may increase the risk of various cancers, including colorectal cancer. This association may be due to a combination of factors such as the content of fat, protein, iron, and/or meat preparation (e.g., cooking or preserving methods). Red meat may be associated with colorectal cancer by contributing to N-nitroso compound (NOC) exposure. Humans can be exposed to NOCs by exogenous routes (from processed meats in particular) and by endogenous routes. Endogenous exposure to NOCs is dose-dependently related to the amount of red meat in the diet. Laboratory results have shown that meats cooked at high temperatures contain other potential mutagens in the form of heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). To investigate the role of these compounds, we have created separate databases for HCAs and PAHs, which we have used in conjunction with a validated meat-cooking food frequency questionnaire. The role of meat type, cooking methods, doneness levels, and meat-cooking mutagens has been examined in both case-control studies and prospective cohort studies, with mixed results. Here, we review the current epidemiologic knowledge of meat-related mutagens, and evaluate the types of studies that may be required in the future to clarify the association between meat consumption and colorectal cancer.

Association of apolipoprotein E polymorphisms and dietary factors in colorectal cancer

“…In addition, heme also damages colonic mucosa and stimulates epithelial proliferation in animal models (Sesink et al, 1999). Red meat diet also leads to the formation of hetrocyclic amines and the endogenous formation of N-nitroso compounds (NOCs) (Cross and Sinha, 2004), which are known potent and organ-specific carcinogens (Magee and Barnes, 1956;Preussmann, 1984). Rats that were fed red meat diets showed significantly greater amounts of DNA single-strand breaks, double-strand breaks, and colonic mucous layer thinning than rats that were fed white meat diet (Toden et al, 2007).…”

Mechanisms Linking Colorectal Cancer to the Consumption of (Processed) Red Meat: A Review

“…In animal studies, both types of compounds have been shown to be carcinogenic through the induction of mutations (de Kok and van Maanen, 2000;Goldman and Shields, 2003;Cross and Sinha, 2004).…”

“…In case meat is grilled over a direct flame, fat/meat juices often drip onto the hot fire, yielding flames containing a number of PAHs which can adhere to the surface of the food. However, PAHs can also be produced during the curing and the processing of the food, for example, when smoking is used as a preservation method (Phillips, 1999;Cross and Sinha, 2004 (IARC, 2013). PAHs are not genotoxic as such, but are activated through metabolization.…”

“…For these reasons, HCAs are generally not considered very important in relation to the carcinogenic properties of meat (Corpet, 2011). Furthermore, as HCAs require metabolic activation to function as mutagens/carcinogens, the carcinogenic potential of HCA may depend on the extent of metabolization (Cross and Sinha, 2004). Cancer risk posed by dietary HCAs was indeed shown to vary with genetic differences in the drug metabolizing enzymes involved e.g.…”

“…In contrast, N-nitrosamines require metabolic activation to be mutagenic and have thus the potential to cause damage at any activation site. During food consumption, humans can be exposed to NOCs both of exogenous and endogenous origin (Cross and Sinha, 2004;J€ agerstad and Skog, 2005).…”