Assessment of N-acetyltransferase 2 (NAT2) gene polymorphisms in bladder cancer patients

Abstract

Introduction: Bladder cancer is the most common cancer of the urinary tract. Aromatic amines are incriminated in the pathogenesis of bladder cancer. While many people are exposed to it, only a small proportion of the exposed individuals develop bladder cancer indicating the contribution of genetic variation, namely N-acetyltransferases (NATs) phenotypes (slow and fast acetylator) which are involved in detoxification of aromatic amines and other carcinogenic toxins. Slow acetylators are less efficient in metabolizing aromatic amines, increased toxic burden and subsequently carcinogenesis. Objectives: The aim of this study was to determine whether NAT2 gene polymorphisms (M1, M2 and M3) are associated with bladder cancer formation and with high stage and grade of the tumor. Patients and Methods: This study was conducted on 35 Egyptian bladder cancer patients. Patients further subdivided according to tumor stage and grade. Fifteen patients with benign renal diseases as a pathological control group, in addition to 15 apparently healthy subjects as a healthy control group included in the study. Assay of NAT2 gene single nucleotide polymorphisms (SNPs) was conducted by polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP) technique. Results: Regarding the frequency of NAT2 gene polymorphism, our study revealed that M1 (C481T) mutation was significantly more frequent in patients than controls groups, however no significant differences with M2 or M3 was seen. Conclusion: This investigation implies that NAT2 genotype exhibit no association with the risk of developing bladder cancer, either alone or with smoking. Moreover, there was no association between NAT2 polymorphism and different stages and grades of bladder cancer.

Keywords

• Bladder cancer
• gene polymorphisms
• Carcinogenic toxins
• Slow acetylator phenotype
• N-acetyltransferases phenotypes
• Cigarette