Abstract
Cytochrome P450 1A1 is a major enzyme in the bioactivation of exogenous procarcinogens
of hepatocellular carcinoma (HCC). However, the contribution of common genetic variants
in CYP1A1 to the HCC risk in Chinese populations has not been thoroughly investigated. In this
study, we examined the association between HCC and four selected tagging single nucleotide
polymorphisms (SNPs) of CYP1A1, and the risk of CYP1A1 haplotypes/diplotypes in 1006 pathologically confirmed HCC patients and 1015 cancer-free
controls, from a Han Chinese population. Haplotypes/diplotypes were constructed from
observed genotypes using the Haplo.Stats program. Relative risk was estimated by using
multivariable logistic regression method. To summarise, we detected an increased HCC
risk in rs4646421 variant carriers (OR 1.30, 95% CI 1.05–1.61) and rs2198843 variant
carriers (OR 1.33, 95% CI 1.05-1.69), and a reduced risk of HCC (OR 0.70. 95% CI 0.52–0.94)
associated with homozygote carriers of rs4886605 variant. These association signals
were also observed in non-smokers with rs4646421 (OR 1.56, 95% CI 1.16–2.08) and rs4886605
(OR 0.61, 95% CI 0.40–0.91). Compared to the most common CYP1A1 haplotype CCAG, the haplotype TTGC conferred an increased risk of HCC (OR 1.26, 95%
CI 1.04–1.52). Similarly, the TTGC/TTGC diplotype conferred an increased risk of HCC
compared with diplotype CCAG/CCAG (OR 2.06, 95% CI 1.23–3.45, P = 0.006). Interestingly, the diplotype TTAC/CCAG also conferred an increased risk of
HCC (OR 1.76, 95% CI 1.22–2.54, P = 0.003). Our results suggested that common genetic variants in CYP1A1 may modulate the risk of developing HCC in the study population, particularly in
non-smokers. However, our findings need to be validated in at least one independent
study of Han Chinese population.
Keywords
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Article info
Publication history
Published online: December 25, 2008
Accepted:
November 7,
2008
Received in revised form:
October 29,
2008
Received:
August 27,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
