Impact of N-acetyltransferase polymorphism (NAT2) in hepatocellular carcinoma (HCC)--an investigation in a department of surgical medicine.
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.
Farker
Katrin
K
Institute of Clinical Pharmacology, Friedrich Schiller University Jena, Germany.
Schotte
Uwe
U
Scheele
Johannes
J
Hoffmann
Annemarie
A
D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D016172:DNA Fingerprinting; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012907:Smoking
D001191:Arylamine N-Acetyltransferase