Genetic Analysis of the Arylamine N-Acetyltransferase Polymorphism in Breast Cancer Patients

Abstract

The association of the arylamine N-acetyltransferase polymorphism and breast cancer has been investigated by analysis of genomic DNA from 160 breast cancer patients and 132 healthy women. Five mutations of the NAT2 gene were studied by using allele-specific PCR amplification and restriction mapping with the endonucleases FoKI and Ddel. Eight allelic variants of the NAT2 gene were identified in both, patients with breast cancer and control groups, with relative frequencies. Wild-type 0.194 and 0.219, 341C+481T+803G 0.433 and 0.345, 341C+481T 0.048 and 0.076, 282T+590A 0.205 and 0.222, 282T 0.059 and 0.044, 590A 0.011 and 0.024, 803G 0.016 and 0.052, 857A 0.035 and 0.019, respectively. The prevalences for the poor acetylator genotypes were 53 and 51 % for the patients with breast cancer and the control group, respectively. Seven patients with the rare lobular breast cancer showed reduced frequency for NAT2 mutations (p < 0.05) and all of them had the extensive acetylator genotype (p < 0.01). This preliminary observation suggests that extensive acetylation may be related to lobular breast cancer. No genetic support for association of the NAT2 polymorphism and other histologic types of breast cancer was found. Any differences in the acetylator rate between breast cancer patients and healthy subjects may be secondary to breast cancer itself, but not involved in the pathogenesis of the disease.

Polymorphisms of Human N-Acetyltransferases and Cancer Risk

“…Shortly afterwards, three phenotyping studies with larger sample sizes reported negative findings [34][35][36]. The first NAT2 genotyping study in patients with breast cancer was published in 1995 and indicated no association of NAT2 polymorphisms and cancer risk [37]. Since then, several studies have addressed the role of NAT polymorphism alone, and the interaction of polymorphisms with smoking in breast cancer risk.…”

Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility

“…145 The population frequency of the fast acetylator genotype of the NAT2 gene is 22-78%. [145][146][147] None of seven studies found an increased breast cancer risk for the slow acetylator NAT2 phenotype, [148][149][150][151][152][153][154] while two studies found a decreased breast cancer risk. 148 153 No association with breast cancer risk was found when all studies were combined.…”

NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis

“…Many studies have evaluated the potential role of NAT2 genotypes in breast cancer development and the risk modification of the effect of smoking on breast cancer by the polymorphisms of this gene . Agundez et al firstly reported that the rapid acetylator NAT2 genotypes might be associated with a risk to develop lobular breast cancer, but no support for an association between NAT2 polymorphisms and breast cancer risk was provided [8]. Conversely, Ambrosone et al reported that breast cancer risk was specifically increased in postmenopausal women with the slow acetylator NAT2 genotypes [9].…”