Abstract LB-408: NAT2 polymorphisms, tobacco smoking, and breast cancer risk in the Breast and Prostate Cancer Cohort Consortium (BPC3)

Abstract

Abstract Aromatic and heterocyclic amines are carcinogens in tobacco smoke that cause mammary tumors in rodents. N-acetyltransferase 2 (NAT2) can detoxy aromatic amines and polymorphisms in the NAT2 gene result in slow, intermediate and rapid acetylation phenotypes. Slow NAT2 acetylation has been hypothesized to potentiate the risk of smoking for both breast and bladder cancer. Whereas this hypothesis is reasonably well-established for bladder cancer, the data for breast cancer are still being evaluated, most recently in a meta-analysis of up to 13 studies. In a subset of these studies including 4,264 cases, a ∼1.4 fold increase in risk of breast cancer was observed among women exposed to more than 20 pack-years of cigarette smoking. This increase in risk was confined to slow acetylators, and no statistically significant increase in risk was observed among rapid acetylators. We sought to replicate this finding in a consortium of six large prospective cohorts in the United States and Europe. We genotyped the three most common polymorphisms that define NAT2 acetylation phenotype in populations of European origin among approximately 7,750 breast cancer cases and 9,900 matched controls with prospectively collected information on tobacco smoking and established risk factors for breast cancer. Nested case-control analyses showed no association between NAT2 acetylation phenotype (rapid, intermediate, slow) and breast cancer risk. Furthermore, no interaction was observed between smoking status (specifically never, former or current) and NAT2 acetylation phenotype on breast cancer risk (likelihood ratio test p-interaction 0.58). Ongoing analyses are examining more detailed measures of cigarette smoking such as duration, intensity, pack years, and smoking during the potentially critical period between menarche and first full term pregnancy, as well as subsets of patients defined by menopausal or steroid hormone receptor status. These data contribute substantially to resolving the longstanding debate over whether smoking affects breast cancer risk particularly in women with limited capacity to acetylate tobacco carcinogens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-408.