RT Journal Article
SR Electronic
T1 Role of <em>N</em>-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 703
OP 709
DO 10.1136/gut.47.5.703
VO 47
IS 5
A1 M-W Yu
A1 C-I Pai
A1 S-Y Yang
A1 T-J Hsiao
A1 H-C Chang
A1 S-M Lin
A1 Y-F Liaw
A1 P-J Chen
A1 C-J Chen
YR 2000
UL http://gut.bmj.com/content/47/5/703.abstract
AB 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 ofNAT1 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 theNAT2*4 allele just failed to reach statistical significance (p=0.06). No association betweenNAT1 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.HBVhepatitis B virusHBsAghepatitis B surface antigenHCChepatocellular carcinomaNATN-acetyltransferaseORodds ratioPCR-RFLPpolymerase chain reaction-restriction fragment length polymorphism