Association of NAT2 and smoking in relation to breast cancer incidence in a population-based case-control study (United States)

Objective: To evaluate the potential interaction between N-acetyltransferase 2 (NAT2) and smoking in breast cancer incidence. Methods: The data are derived from a population-based case–control study of women aged 20–69 years who were residents of Massachusetts or Wisconsin during 1997–1998. Incident cases of invasive breast cancer were identified through state tumor registries and age-similar controls were selected at random from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors including smoking history. Women provided oral mucosal DNA through the mail for genetic studies. Results: A total of 791 cases and 797 controls were included in the analysis. Overall, smoking was modestly associated with breast cancer risk (multivariate odds ratio (OR) for ever smoking: 1.37; 95% confidence interval (CI): 1.12–1.69), and there was a trend in risk for greater pack-years of smoking among postmenopausal women (p for trend = 0.02). Overall, NAT2 was not related to invasive breast cancer (multivariate OR: 1.11; 95% CI: 0.90–1.36). Associations of smoking with breast cancer tended to be somewhat stronger among the women with the slow acetylator genotype for NAT2: when compared to those who never smoked and were rapid acetylators, the OR for ever smoking was 1.50 (95% CI: 1.11–2.02) in slow acetylators, and OR: 1.24 (95% CI: 0.91–1.70) in rapid acetylators. However, tests for multiplicative interaction were not significant in case–control comparisons, or in case-only analyses. Conclusion: Results of the study are compatible with the majority of previous studies that indicate little or no association of NAT2, smoking, or their interaction with the occurrence of breast cancer.