Association between N-acetyltransferase 2 (NAT2) genetic polymorphism and development of breast cancer in post-menopausal Chinese women in Taiwan, an area of great increase in breast cancer incidence

Abstract

The incidence of breast cancer has increased greatly in Taiwan over the past 2 decades. Increased exposure to environmental carcinogens, including aryl aromatic amines, as a result of the economic boom, is suspected to be one factor contributing to this increase. The enzyme N-acetyl-transferase 2 (NAT2) determines the rate of metabolism of aryl aromatic amines, and therefore the NAT2 slow acetylator genotype is associated with an increased risk of cancer. Our present case-control study of 150 breast cancer patients and 150 healthy controls in Taiwan was performed to explore the association between NAT2 genetic polymorphism and individual susceptibility to breast cancer. A structured questionnaire was used to collect relevant information regarding all known or suspected risk factors of breast cancer. The NAT2 genotype was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 139 cases and 133 controls, and 28.8% and 21.1%, respectively, were found to have slow acetylator genotypes. Multivariate analysis, simultaneously considering other risk factors, including age at menarche, nulliparity or age at first full-term pregnancy, body mass index (BMI), hormone replacement therapy (HRT) and smoking status, showed that the NAT2 slow acetylator genotype was associated with an increased risk with borderline significance (Odds Radio, 1.81; 95% C1, 1.01-3.31). Interestingly, this association was not significance in premenopausal women, but was significant in post-menopausal women. Further stratification of our study subjects based on different risk factor status showed that the increased risk for an NAT2 slow acetylator was more marked in post-menopausal women who were not using HRT or who had a lower BMI. Our findings suggest that NAT2 polymorphism is a susceptibility factor for breast cancer in Taiwanese women, and that NAT2-metabolized carcinogens are probably present in the environment and may be associated with induction of breast cancer.