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Epidemiology/Lifestyle Factors: Diet and Cancer 2

Is the association between flame-broiled food, meat consumption, and breast cancer modified by N-acetyltransferases and aspirin use?

Johns Hopkins University, Baltimore, MD; Mercy Medical Center, Baltimore, MD; National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, NC; Medical University of South Caroilina, Charleston South Carolina, SC

Abstract

B159

Background: Heterocyclic amines (HCA) are pro-carcinogens produced when meat is cooked in direct heat, such as flame-broiled (FB) food. The N-acetyltransferases (NAT) are enzymes involved in the activation of HCAs. Laboratory data suggest that aspirin may inhibit NAT activity. Methods: In a population based nested case-control study, we assessed the association between flame-broiled food, meat consumption and the risk of breast cancer and whether it varies by NAT2 genotype status or aspirin intake in 312 cases and 316 controls. Genotyping for rapid, intermediate and slow metabolizers of NAT2 was carried out on three NAT2 alleles. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from logistic regression models. The median intake level among controls was used as the cut point for meat consumption. Results: Breast cancer risk was significantly elevated among women who ate FB food greater than twice a month compared to women who never ate FB (O.R. 1.74, 95% CI 1.04, 2.89). Meat consumption of greater than 64 grams/day compared to less than or equal to 64 grams/day was also associated with a higher breast cancer risk (O.R.1.43, 95% CI 1.01, 2.01). Independent of food intake, rapid acetylators of NAT2 were at increased risk for breast cancer compared to slow acetylators, but the association was not statistically significant (O.R.1.82 95% CI 0.93, 3.56). Further, rapid acetylators who ate FB food or consumed more than 64 gram/day of meat were more likely to develop breast cancer than slow acetylators who never ate flame-broiled food (O.R. 1.86, 95% CI 1.10, 3.15) or consumed less than or equal to 64 grams/day of meat (O.R.1.69, 95%CI 1.04, 2.75). Among this risk group (rapid acetylators consuming FB food or more than 64 gram/day of meat) aspirin use completely attenuated the observed risk. Conclusion: Our results suggest that NAT2 acetylator status and aspirin intake may be important determinants of the effect of HCAs on the breast carcinogenesis pathway.