Genetic polymorphism of N acetyltransferase 2 and its association with tumor markers and cigarette smoking in hepatocellular carcinoma

Abstract

Human N-acetyltransferase 2 (NAT2) is polymorphic and may associate with cancer risk by modifying susceptibility to cancers from carcinogen  exposure. NAT2 capacity varies in humans and is often subdivided into rapid and slow acetylator phenotypes. This study aimed to describe the genetic pattern of NAT2 in hepatocellular carcinoma patients and detecting if there is variation of the pattern of polymorphism compared to liver  cirrhotic patients and normal healthy controls. This study included 50 newly diagnosed untreated hepatocellular carcinoma patients, 25 patients having liver cirrhosis and 25 age and sex- matched healthy subjects as a control group. All subjects were investigated for liver function tests, tumor markers
[Alfa-fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and CA19-9] and NAT-2 genotyping using PCR-RFLP technique. The results of this study  revealed high prevalence of slow acetylator phenotype in HCC (56%) and cirrhotic (68%) groups versus 16 % in control group. However, the rapid acetylator was the highly prevalent phenotype among the control group (56%) versus (8%) for each of HCC and cirrhotic groups. Of note, one of slow acetylator phenotypes (M3/NAT2*7) was only detected in HCC cases (22%) and AFP levels were significantly higher in those cases. Moreover, 40% of HCC patients were heavy smokers, 85% of them showed to have NAT2 slow acetylator phenotype, which could suggest a role of smoking in HCC. These results suggest that NAT2 polymorphism may exert a strong effect on individual susceptibility to HCC particularly in heavy smokers. NAT2*7 phenotype showed a significant correlation with HCC cases and should be further studied. Also, NAT-2 polymorphism pattern should be studied on a larger scale to know its distribution in the Egyptian  population.

Keywords: NAT2 polymorphism, HCC, smoking, tumor markers .