Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: Impact of smoking on risk
Journal
Gut
Journal Volume
47
Journal Issue
5
Pages
703-709
Date Issued
2000
Author(s)
Abstract
Background - Persistent infection with hepatitis B virus (HBV) causes chronic phasic necroinflammation and regenerative proliferation in the liver. The sustained hepatocellular proliferation may render chronic HBV carriers more susceptible to the effects of environmental carcinogens. Aromatic amines are potential hepatocarcinogens in humans. N-acetyltransferase (NAT) is involved in the metabolic activation and detoxification of these compounds. Aims - To investigate if genetic polymorphisms in N-acetylation are related to hepatocellular carcinoma (HCC) among chronic HBV carriers. Methods - Genotyping of NAT1 and NAT2 was performed using polymerase chain reaction-restriction fragment length polymorphism on peripheral leucocyte DNA from 151 incident cases of HCC and 211 controls. All subjects were male, and were chronic HBV surface antigen carriers. Results - A significant association between NAT2 genetic polymorphism and HCC was observed among chronic HBV carriers who were smokers but not among those who were non-smokers. For smoking HBV carriers, the odds ratios of developing HCC for those heterozygous and homozygous for the NAT2*4 functional allele compared with those without any copies of the functional allele (reference group) were 2.67 (95% confidence interval 1.15-6.22) and 2.58 (95% confidence interval 1.04-6.43), respectively. The interaction between cigarette smoking and the presence of the NAT2*4 allele just failed to reach statistical significance (p=0.06). No association between NAT1 genotype and HCC was evident overall or within the smoking stratified subgroups. Conclusions - Our results suggest that NAT2 activity may be particularly critical in smoking related hepatocarcinogenesis among chronic HBV carriers. Our data also indirectly support a role for tobacco smoke derived aromatic amines in the aetiology of HCC.
Subjects
Genetic polymorphism; Hepatocellular carcinoma; N-acetyltransferase; Smoking
SDGs
Other Subjects
acyltransferase; aromatic amine; hepatitis B surface antigen; tobacco smoke; adult; allele; article; cancer risk; cigarette smoking; controlled study; enzyme activity; enzyme polymorphism; genotype; hepatitis B; Hepatitis B virus; heterozygote; homozygote; human; liver carcinogenesis; liver cell carcinoma; major clinical study; male; polymerase chain reaction; priority journal; restriction fragment length polymorphism; risk factor; virus carrier
Publisher
BMJ Publishing Group
Type
journal article