A Case-Only Analysis of the Interaction between N-Acetyltransferase 2 Haplotypes and Tobacco Smoke on Breast Cancer Etiology

INTRODUCTION. N-acetyltransferase 2 is a polymorphic enzyme in humans. Women who possess homozygous polymorphic alleles have a slower rate of metabolic activation of aryl aromatic amines, one of the constituents of tobacco smoke that has been identified as carcinogenic. We hypothesized that women with breast cancer who were slow acetylators would be at increased risk of breast cancer associated with active and passive exposure to tobacco smoke. METHODS. We used a case-only study design to evaluate departure from multiplicativity between acetylation status and smoking status. We extracted DNA from buccal cell samples collected from 502 women with incident primary breast cancer and assigned acetylation status by genotyping ten single-nucleotide polymorphisms. Information on tobacco use and breast cancer risk factors was obtained by structured interviews. RESULTS. We observed no substantial departure from multiplicativity between acetylation status and history of ever having been an active smoking (adjusted odds ratio estimate of departure from multiplicativity = 0.9, 95% confidence interval 0.5 to 1.7) or ever having had passive residential exposure to tobacco smoke (adjusted odds ratio = 0.7, 95% confidence interval 0.4 to 1.5). The estimates for departure from multiplicativity between acetylation status and various measures of intensity, duration, and timing of active and passive tobacco exposure lacked consistency and were generally not supportive of the idea of a gene–environment interaction. CONCLUSION. In this, the largest case-only study to evaluate the interaction between acetylation status and active or passive exposure to tobacco smoke, we found little evidence to support the idea of a departure from multiplicativity.National Institutes of Health, National Cancer Institute (K07 CA87724); National Institutes of Health, National Institute of Environmental Health Sciences (2P42 ES07381); Environmental Protection Agency; National Institutes of Health, National Institute on Aging & National Cancer Institute (R01 CA/AG70818