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In the multifactorial aetiology of hepatocellular carcinoma (HCC), an association and interaction between genetic polymorphisms of xenobiotic metabolizing enzymes, lifestyle factors, and cancer risk has been postulated. N-acetyltransferase (NAT2) is involved in the metabolic activation and detoxification of aromatic amines. Aromatic amines are potential hepatocarcinogens in humans. In the present study, we investigated if genetic NAT2 polymorphism is related to HCC. Genotyping of NAT2 was performed in 70 HCC patients and 87 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results of this investigation show that 46 out 70 HCC patients (65.7%) and 50 out of 87 controls (57.5%) were of the slow acetylator genotypes. The frequency of distribution of slow and rapid acetylators (genotypes) was not significantly different between cases and controls (p > 0.05). Slow acetylator genotypes were not associated with a significantly increased HCC risk (odds ratio, 1.4; 95% confidence interval, 0.74-2.72). A significant association between NAT2 genetic polymorphism and HCC was observed among smokers. Slow acetylator genotypes significantly increased the HCC risk in cigarette smokers (odds ratio, 3.5; 95% confidence interval, 1.38-9.05). Our results suggest that genetic NAT2 polymorphism may play a role in lifestyle factors-related hepatocarcinogenesis. NAT2 activity may be particulary critical in smoking related hepatocarcinogenesis.

The pathogenesis of human hepatocellular carcinoma (HCC) is a multistage process with the involvement of a multifactorial etiology. The role of drugs as risk factors has not been conclusively ascertained, but it appears that the use of oral contraceptives can be included. In the multifactorial etiology of human hepatocellular carcinoma (HCC), an association and interaction between genetic polymorphisms of xenobiotic metabolizing enzymes, lifestyle factors and cancer risk has been postulated. This pilot investigation examines the frequency of polymorphisms in selected genes (NAT2, CYP2E1) coding for xenobiotic metabolizing enzymes, and life-style habits (cigarette smoking, alcohol consumption) in 38 HCC patients. Genotyping of xenobiotic metabolizing enzymes was carried out using polymerase chain reaction--restriction fragment length polymorphism methods and DNA extracted from peripheral blood cells. In addition, HCC patients were interviewed with regard to their cigarette smoking habits and alcohol consumption using a standardized questionnaire. The results of this pilot investigation showed that the majority of the HCC patients smoke and consume alcohol. We found no predominance of slow acetylators (45%) or rapid acetylators (55%). 70.6% of slow acetylators were smokers. 86.5% of all patients with homozygote PstI/RsaI genotype also carried the homozygote DraI genotype, whereas 10.8% of all subjects with heterozygote PstI/RsaI genotype also carried the heterozygote DraI genotype. These genotype frequencies remain to be confirmed in a larger ethnic group. Whether polymorphisms of xenobiotic metabolizing enzymes is an important risk factor in (cigarette smoking-/alcohol consumption) HCC or not is currently being investigated in a case-control study in the same ethnic group.