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Heterocyclic amines (HCAS) and risk of breast cancer

HCAs are mutagenic and carcinogenic compounds formed in meat and fish prepared by high-temperature cooking methods, such as frying, grilling and barbecuing. The precursors are amino acids, reducing sugars and creatine, found specifically in muscle meat. One of the HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant HCA in the Western diet, has been found to be a mammary gland carcinogen in rats. Studies in rodents have also shown that PhIP is distributed to the mammary gland and excreted into breast milk. Several epidemiologic studies have found a moderately increased risk of breast cancer with higher intake of red meat. Zheng et al (JNCI 1998) conducted a case-control study within the cohort of the Iowa Women's Health Study to investigate the potential role of meat and HCAs and the risk of breast cancer. A questionnaire was mailed to women in the cohort who had breast cancer diagnosed during the period from 1992 to 1994, and to a random sample of cancer-free cohort members to obtain information on usual intake of meats and cooking practices. Color photographs showing various levels of doneness for hamburger, beefsteak, and bacon were included. Using a HCA database (Sinha et al: Food Chem Toxicol 1998), dietary intake of 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3, 4, 8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and PhIP were estimated. Multivariate analysis was performed on data from 273 cases and 657 control subjects who completed the survey. Well-done red meat intake was associated with increased risk of breast cancer (Zheng et al: JNCI 1998). The odds ratios (95% confidence interval) for categorical analysis of PhIP, with first quintile as the referent group, were as follows: second quintile 1.1 (0.6-1.8); third quintile 1.2 (0.7-1.9); fourth quintile 1.4 (0.8-2.3); and fifth quintile 1.9 (1.1-3.4) - P value for trend 0.001 (Sinha etal: JNCI 2000). There was no statistically significant increase in risk with either MeIQx or DiMeIQx. Both animal carcinogenicity studies and epidemiologic evidence suggests that consumption of PhIP may increase the risk of breast cancer, but this hypothesis needs to be investigated further. Simple changes in cooking methods could eliminate the presence of PhIP in foods, if it is conclusively found to increase the risk of breast cancer.

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Sinha, R., Snyderwine, E. Heterocyclic amines (HCAS) and risk of breast cancer. Breast Cancer Res 3 (Suppl 1), A60 (2001).

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