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Br J Cancer. 1999 May;80(3-4):598-603.

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

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1
School of Public Health and Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei.

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 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 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 Mspl 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 Mspl and Ile-Val polymorphisms of CYP1A1 may have different mechanisms for increasing susceptibility to smoking-related HCC.

PMID:
10408872
PMCID:
PMC2362308
DOI:
10.1038/sj.bjc.6690397
[Indexed for MEDLINE]
Free PMC Article
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