Abstract
B63
Background >Heterocyclic amines (HCA) are pro-carcinogens produced when meat is cooked in direct heat such as flame-broiled food. The N-acetyltransferases are enzymes involved in the activation of HCAs, whereas glutathione S-transferases (GSTs) are thought to protect individuals from the genotoxic effects of carcinogens such as HCAs. We previously reported an association between NAT2 acetylator status, flame-broiled food and breast cancer and now examine differences by polymorphisms in genes encoding the GSTs. Methods: In a population based nested case-control study of 321 cases and matched controls we examined whether the association between breast cancer risk and flame-broiled (FB) food intake and meat consumption varied by both GSTM1 and GSTT1 copy number or NAT2 acetylator status. Characterization of rapid, intermediate and slow metabolizers of NAT2 was based on three NAT2 alleles. Quantitative TaqMan copy number assays were used to determine GSTM1 and GSTT1 copy number. 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: Twenty percent of controls had both GSTT1 alleles absent, 53% both GSTM1 alleles absent, and 10% absent alleles in both genes Women with absent GSTT1 alleles who ate FB food or consumed more than 64 grams/day of meat were more likely to develop breast cancer than those with at least one GSTT1 allele who never ate flame-broiled food (O.R. 2.53, 95% CI 1.28, 4.97) or consumed less than or equal to 64 grams/day of meat (O.R.2.13, 95%CI 1.06, 4.27). The odds of developing breast cancer was also increased in women with absent GSTM1 alleles who ate FB food or consumed more than 64 gram/day of meat when compared to those with at least one GSTM1 allele who never ate flame-broiled food (O.R. 2.11, 95% CI 1.20, 3.70) or consumed less than or equal to 64 grams/day of meat (O.R.2.46, 95%CI 1.40, 4.32). In addition breast cancer risk was largely attenuated among rapid acetylators of NAT2 who also inherited 1 or more GSTM1 or GSTT1 alleles. >Conclusion: Our results suggest that in addition to NAT2 acetylator status the protective role of GST's, in particular GSTM1 and GSTT1 may be an important determinant of the effect of HCAs on breast cancer risk.
Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA