Assessment of frequencies of lifestyle factors and polymorphisms of drug-metabolizing enzymes (NAT2, CYP2E1) in human hepatocellular carcinoma (HCC) patients in a department of surgical medicine - a pilot investigation

The pathogenesis Of human hepatocellular carcinoma (HCC) is a multi-stage process with the involvement of a mulit-factorial 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 polymorssphisms 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 lifestyle 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 I this pilot investigation showed that the majority of the HCC patient,, 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.