Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus-associated hepatocellular carcinoma.

BACKGROUND: The carcinogenic process can be modulated by exposure to endogenous or environmental substance(s) acting as carcinogens or protocarcinogens. Polymorphic enzymes of cytochrome P450 (CYP) that play a role in detoxication/toxication of such substances via metabolization may account for the interpatient variability of clinical course in cancers such as hepatocellular carcinoma (HCC). Many CYP genetic polymorphisms, which may change enzyme activity, are known to exist in Japanese. The aim of the present study was to compare the frequencies of CYP polymorphisms between hepatitis C virus (HCV)-related HCC patients and healthy subjects.

METHODS: Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. These mutant alleles have been reported to change the CYP enzyme activity in Japanese. The frequencies of the mutant alleles and genotypes were then compared with those reported in healthy Japanese.

RESULTS AND CONCLUSION: There is no statistically significant difference in genetic mutant alleles between the two groups, except for the genotype of CYP2A6*4A homozygous. The frequency of this genotype in the HCC patients (0.144) is significantly higher than that in healthy Japanese (0.034; P < 0.05; odds ratio 3.36). The clinical significance related to HCC is unknown. Further evaluation of CYP2A6*4A (deletion type) in HCV-related HCC patients is required.