Cytochrome P450 1A1 genetic polymorphisms and risk of hepatocellular carcinoma among chronic hepatitis B carriers

Cigarette smoking has been associated with increased risk of hepatocellular carcinoma (HCC) in some epidemiological studies. Cytochrome P450 1A1 (CYP1 A1) is involved in the biotransformation of tobacco-derived polycyclic arom atic hydrocarbons (PAHs) into carcinogenic metabolites. The aim of this stu dy was to determine whether CYP1A1 polymorphisms were related to HCC risk a mong chronic hepatitis B virus (HBV) carriers. Genotypic variants of CYP1A1 were determined using polymerase chain reaction in 81 incident cases of HC G and 409 controls nested in a cohort study of 4841 male chronic HBV carrie rs. No overall association between CYP1A1 genotypes and HCC was observed. T he presence of the Mspl (odds ratio (OR) 3.15, P = 0.0196) or Ile-Val (OR 1 .99, P = 0.0855) variant allele of CYP1A1 increased HCC risk among smokers, but posed no increased risk among non-smokers. The smoking-related HCC ris k was most pronounced among those who had a susceptible allele of the CYP1A 1 and a deficient genotype of glutathione S-transferase M1, which detoxifie s PAH electrophilic metabolites produced by CYP1A1. In the absence of the I le-Val variant allele, the Mspl polymorphism was still associated with smok ing-related HCC. This study suggests that tobacco-derived PAHs play a role in HCC risk among chronic HBV carriers, and CYP1A1 polymorphism is an impor tant modulator of the hepatocarcinogenic effect of PAHs. The Mspl and Ile V al polymorphisms of CYP1A1 may have different mechanisms for increasing sus ceptibility to smoking-related HCC.