Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The relative risk of colon cancer was 1.18 (95% CI: 1.06–1.32) for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative precancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicity. Cancer Prev Res; 4(2); 177–84. ©2011 AACR.
Cancer of the colon and rectum, taken together, are the third most common type of cancer worldwide (1). In most publications, colon and rectal cancer are studied together and the term colorectal cancer (CRC) is used, which we also use here, except when the publications refer specifically to colon or rectal cancer. CRC is the second most common cause of cancer death in affluent countries. Dietary modifications might reduce this cancer burden by up to 70% (2). Three recent meta-analyses showed that total meat intake is not related to risk but that intake of red or processed meat is associated with a modest, but significant risk of CRC (3–5). Processed meat intake appears to be more closely linked with the risk of CRC than fresh red meat intake. In its 2007 report, the World Cancer Research Fund panel recommended that one should limit intake of red meat and avoid processed meat (1).
Several mechanisms may explain the relationship between the risk of CRC and the intake of red or processed meat. First, meat cooked at high temperature contains mutagenic heterocyclic amines. But heterocyclic amines might not be major players in CRC risk, as: (i) consumption of chicken is a major contributor to intake of heterocyclic amines, but is not associated with the risk (6); and (ii) doses of heterocyclic amines that induce cancer in animals are 1,000 to 100,000 times higher than the dose ingested by humans (7). A second hypothesis suggests that the high saturated fat content of red and processed meat increases the risk of CRC. But several studies, including a recent meta-analysis, showed no effect of saturated fat on colorectal carcinogenesis (8–11). A third hypothesis concerns the carcinogenic N-nitroso compounds (NOC), which can be formed in the gastrointestinal tract by N-nitrosation of peptide derived amines or amides. The role of NOC in human cancer is discussed in the following text. Other more unlikely hypotheses involve the high protein, cholesterol, and salt content of red or processed meat. For a review of all these mechanisms, see ref. 12.