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

被引：0
作者：
M-W Yu
Y-H Chiu
S-Y Yang
R M Santella
H-D Chern
Y-F Liaw
C-J Chen
机构：
[1] School of Public Health,Division of Environmental Health Sciences
[2] National Taiwan University,undefined
[3] Graduate Institute of Epidemiology,undefined
[4] College of Public Health,undefined
[5] National Taiwan University,undefined
[6] School of Public Health,undefined
[7] Columbia University,undefined
[8] Graduate Institute of Pharmaceutical Sciences,undefined
[9] College of Medicine,undefined
[10] National Taiwan University,undefined
[11] Liver Research Unit,undefined
[12] Chang-Gung Memorial Hospital and Chang-Gung Medical College,undefined
来源：
British Journal of Cancer | 1999年 / 80卷
关键词：
chronic hepatitis B virus carriers; cigarette smoking; cytochrome P450 1A1; glutathione S-transferase M1; hepatocellular carcinoma; nested case-control study;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
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页码：598 / 603
页数：5
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