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. 1999 May 1;80(3-4):598–603. doi: 10.1038/sj.bjc.6690397

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

M-W Yu 1,2, Y-H Chiu 2, S-Y Yang 2, R M Santella 3, H-D Chern 4, Y-F Liaw 5, C-J Chen 2
PMCID: PMC2362308  PMID: 10408872

Abstract

Cigarette smoking has been associated with increased risk of hepatocellular carcinoma (HCC) in some epidemiological studies. Cytochrome P450 1A1 (CYP1A1) is involved in the biotransformation of tobacco-derived polycyclic aromatic hydrocarbons (PAHs) into carcinogenic metabolites. The aim of this study was to determine whether CYP1A1 polymorphisms were related to HCC risk among chronic hepatitis B virus (HBV) carriers. Genotypic variants of CYP1A1 were determined using polymerase chain reaction in 81 incident cases of HCC and 409 controls nested in a cohort study of 4841 male chronic HBV carriers. No overall association between CYP1A1 genotypes and HCC was observed. The presence of the MspI (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 risk was most pronounced among those who had a susceptible allele of the CYP1A1 and a deficient genotype of glutathione S-transferase M1, which detoxifies PAH electrophilic metabolites produced by CYP1A1. In the absence of the Ile-Val variant allele, the MspI polymorphism was still associated with smoking-related HCC. This study suggests that tobacco-derived PAHs play a role in HCC risk among chronic HBV carriers, and CYP1A1 polymorphism is an important modulator of the hepatocarcinogenic effect of PAHs. The MspI and Ile-Val polymorphisms of CYP1A1 may have different mechanisms for increasing susceptibility to smoking-related HCC. © 1999 Cancer Research Campaign

Keywords: chronic hepatitis B virus carriers, cigarette smoking, cytochrome P450 1A1, glutathione S-transferase M1, hepatocellular carcinoma, nested case-control study

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Selected References

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