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Dietary Mutagens and the Risk of Breast Cancer

1998; Oxford University Press; Volume: 90; Issue: 22 Linguagem: Inglês

10.1093/jnci/90.22.1687

1460-2105

Kathleen M. Egan, E. Giovannucci,

Radiation Effects and Dosimetry

In this issue of the Journal, Zheng et al. (1) report a positive association between the preference for well-done red meat and risk of postmenopausal breast cancer. Using color photographs of hamburger, bacon, and beefsteak showing increasing levels of doneness (from extremely rare to very well done), women who selected a cooking preference for ‘‘very well done’’ for each of these foods had a risk nearly five times higher than that for women who consistently selected a preference for rare/medium cooking. Overall consumption of red meat itself had only a weak association with risk, and white meats, including chicken, turkey, and fish, were not statistically significant risk factors regardless of cooking method. The specificity of the findings to meat preparation tends to rule out saturated fat as the causative factor and is consistent with the possibility that mutagens, including heterocyclic amines, formed during high-temperature cooking of meats may be mammary carcinogens in humans. The browned and charred surface of meats contains a hash of laboratory carcinogens. Among these are the heterocyclic amines, formed through chemical reactions involving amino acids. The formation of heterocyclic amines requires high temperatures, such as are found in radiative or conductive cooking (e.g., grilling or frying) but not as a rule in indirect convection (e.g., roasting) or boiling (e.g., poaching or steaming) methods (2). These substances are capable of inducing tumors in a number of species (2) and are reportedly among some of the most powerful mutagenic agents, based on the Ames test (3). Heterocyclic amines involving creatinine as a precursor are numerically most important. Among these, 2-amino-1-methyl-6phenylimidazo[4,5-b]pyridine (PhIP) predominates, accounting for approximately one half of the total heterocyclic amine intake in the U.S. diet. Five compounds, i.e., PhIP, 2-amino3,8-dimethylimidazo[4,5-f ]quinoxaline (MeIQx), 2-amino3,4,8-trimethylimidazo[4,5-f]quinoxaline ( DiMeIQx), 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ), and 2-amino9H-pyrido[2,3-b]indole (AaC), make up approximately two thirds of the total intake (4). Based on animal bioassay data, the relative mutagenic potency of these compounds varies by a factor of more than 20, with IQ and DiMeIQx at the high end, PhIP and AaC at the low end, and MeIQx at an intermediate level of potency (4). Thus, the absolute concentration of specific heterocyclic amines in foods must be weighed against their individual potential for genetic damage when they are evaluated as potential human carcinogens. Major dietary sources of these compounds vary from population to population depending on a number of factors, including cultural mores and meat availability. In a study of female registered nurses (5), the major predictor of PhIP in the diet was grilled or broiled chicken, whereas the chief source of DiMeIQx was pan-fried steak.