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
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Primary liver cancer: worldwide incidence and trends.Gastroenterology. 2004; 127: S5-S16
- Global cancer statistics, 2002.CA Cancer J Clin. 2005; 55: 74-108
- Liver transplantation for malignancy.Oncologist. 2005; 10: 269-281
- Hepatocellular carcinoma pathogenesis: from genes to environment.Nat Rev Cancer. 2006; 6: 674-687
- Epidemiological characteristics and risk factors of hepatocellular carcinoma.J Gastroenterol Hepatol. 1997; 12: S294-S308
- Polycyclic aromatic hydrocarbon-DNA adducts in liver tissues of hepatocellular carcinoma patients and controls.Int J Cancer. 2002; 99: 14-21
- Polycyclic aromatic hydrocarbon- and aflatoxin-albumin adducts, hepatitis B virus infection and hepatocellular carcinoma in Taiwan.Cancer Lett. 2007; 252: 104-114
- Modulation of gene expression and DNA-adduct formation in precision-cut liver slices exposed to polycyclic aromatic hydrocarbons of different carcinogenic potency.Mutagenesis. 2007; 22: 55-62
- Structure and drug inducibility of the human cytochrome P-450c gene.Eur J Biochem. 1986; 159: 219-225
- Cytochrome P450 1A1 genetic polymorphisms and risk of hepatocellular carcinoma among chronic hepatitis B carriers.Brit J Cancer. 1999; 80: 598-603
- CYP enzyme polymorphisms and susceptibility to HCV-related chronic liver disease and liver cancer.Int J Cancer. 2003; 104: 310-317
- Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor and GSTM1 polymorphisms.Pharmacogenetics. 2000; 10: 11-24
- Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults.Gut. 2003; 52 Suppl 3: iii1-iii8
- Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium.Am J Hum Genet. 2004; 74: 106-120
- CYP 1A1 polymorphism and risk of lung cancer in relation to tobacco smoking: a case-control study in China.Carcinogenesis. 2001; 22: 11-16
- CYP1A1 and GSTM1 polymorphisms and oral cancer risk.Cancer Epidemiol Biomarkers Prev. 1997; 6: 791-797
- A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other.Am J Hum Genet. 2004; 74: 765-769
- Score tests for association between traits and haplotypes when linkage phase is ambiguous.Am J Hum Genet. 2002; 70: 425-434
- A comparison of bayesian methods for haplotype reconstruction from population genotype data.Am J Hum Genet. 2003; 73: 1162-1169
- Expression of cytochrome P450 1A1 and its contribution to oxidation of a potential human carcinogen 1-phenylazo-2-naphthol (Sudan I) in human livers.Cancer Lett. 2005; 220: 145-154
- The catalytic activity of four expressed human cytochrome P450s towards benzo[a]pyrene and the isomers of its proximate carcinogen.Biochem Biophys Res Commun. 1993; 192: 1373-1379
- A constitutively active dioxin/aryl hydrocarbon receptor promotes hepatocarcinogenesis in mice.Cancer Res. 2004; 64: 4707-4710
- An abundance of bidirectional promoters in the human genome.Genome Res. 2004; 14: 62-66
- A common regulatory region functions bidirectionally in transcriptional activation of the human CYP1A1 and CYP1A2 genes.Mol Pharmacol. 2006; 69: 1924-1930
- Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China.Pharmacogenet Genomics. 2006; 16: 219-227
- Internal genomic sequence of human CYP1A1 gene is involved in superinduction of dioxin-induced CYP1A1 transcription by cycloheximide.Biochem Biophys Res Commun. 2007; 355: 687-692
- FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization.Nucleic Acids Res. 2006; 34: W635-W641
- Overexpression of cytochrome P450 1A1 and its novel spliced variant in ovarian cancer cells: alternative subcellular enzyme compartmentation may contribute to carcinogenesis.Cancer Res. 2005; 65: 3726-3734
- Lung cancer risk and CYP1A1 genotype in African Americans.Carcinogenesis. 1998; 19: 813-817
- Susceptibility to lung cancer in light smokers associated with CYP1A1 polymorphisms in Mexican- and African–Americans.Cancer Epidemiol Biomarkers Prev. 1997; 6: 1075-1080
- Levelling-off of the risk of lung and bladder cancer in heavy smokers: an analysis based on multicentric case-control studies and a metabolic interpretation.Mutat Res. 2000; 463: 103-110
- Genetically based N-acetyltransferase metabolic polymorphism and low-level environmental exposure to carcinogens.Nature. 1994; 369: 154-156
- Dose-response relationship in tobacco-related cancers of bladder and lung: a biochemical interpretation.Int J Cancer. 2004; 108: 2-7
- A genome-wide analysis of admixture in Uyghurs and a high-density admixture map for disease-gene discovery.Am J Hum Genet. 2008; 83: 322-336
- Case-control studies of association in structured or admixed populations.Theor Popul Biol. 2001; 60: 227-237
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.