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-acetyltransferase 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 Ratio, 1.81; 95% CI, 1.01-3.31). Interestingly, this association was not significant 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. Int.

Active and passive smoking, IL6, ESR1, and breast cancer risk

“…In contrast, IL6 interacted with passive smoking, suggesting involvement of inflammation in response to mutagens is stronger from exposure to passive rather than active smoke, although there are limited data examining inflammation-related pathways and breast cancer. However, some but not all studies show that NAT2, CYP1A1, and MnSOD alter smoking-related breast cancer risk [5,12,[42][43][44][45][46][47].…”

The CYP19 TTTA Repeat Polymorphism Is Related to the Prognosis of Premenopausal Stage I–II and Operable Stage III Breast Cancers

“…Most had been invited to take part in our previous molecular epidemiological studies [17][18][19][20], aimed at defining the contribution of genotypic polymorphisms of carcinogen-and estrogen-metabolizing genes as susceptibility factors for breast cancer development in Taiwan. Genomic DNA and detailed demographic information were obtained from the patients with their consent.…”

Breast cancer risk associated with genotype polymorphism of the catechol estrogen‐metabolizing genes: A multigenic study on cancer susceptibility

“…17,18 This and all our previous studies had been approved by the ethics committee of the Institute of Biomedical Sciences, Academia Sinica. Because of the low incidence of breast cancer, which suggests an overall lower effect of common risk factors, and its homogenous genetic background, the Taiwanese population has certain advantages for studying the effects of subtle genetic variations, 20 such as genotypic polymorphisms. Using data from 254 female incident breast cancer patients and 379 healthy female controls recruited between September 2001 and March 2002, we reported recently an association between breast cancer risk and genotypic polymorphisms of the DSBR genes.…”