Common genetic variations of the cytochrome P450 1A1 gene and risk of hepatocellular carcinoma in a Chinese population

Rui Li, Yin Yao Shugart, Weiping Zhou, Yu An, Yuan Yang, Yun Zhou, Beibei Zhang, Daru Lu, Hongyang Wang, Ji Qian, Li Jin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1239-1247
Number of pages9
JournalEuropean Journal of Cancer
Volume45
Issue number7
DOIs
StatePublished - May 2009

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Cytochrome P-450 Enzyme System
Hepatocellular Carcinoma
Cytochrome P-450 CYP1A1
Population
Genes
Haplotypes
Homozygote
Single Nucleotide Polymorphism
Logistic Models
Genotype
Enzymes

Keywords

  • CYP1A1
  • Genetic polymorphism
  • Haplotype
  • Hepatitis
  • Hepatocellular carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Common genetic variations of the cytochrome P450 1A1 gene and risk of hepatocellular carcinoma in a Chinese population. / Li, Rui; Shugart, Yin Yao; Zhou, Weiping; An, Yu; Yang, Yuan; Zhou, Yun; Zhang, Beibei; Lu, Daru; Wang, Hongyang; Qian, Ji; Jin, Li.

In: European Journal of Cancer, Vol. 45, No. 7, 05.2009, p. 1239-1247.

Research output: Contribution to journalArticle

Li, R, Shugart, YY, Zhou, W, An, Y, Yang, Y, Zhou, Y, Zhang, B, Lu, D, Wang, H, Qian, J & Jin, L 2009, 'Common genetic variations of the cytochrome P450 1A1 gene and risk of hepatocellular carcinoma in a Chinese population', European Journal of Cancer, vol. 45, no. 7, pp. 1239-1247. https://doi.org/10.1016/j.ejca.2008.11.007
Li, Rui ; Shugart, Yin Yao ; Zhou, Weiping ; An, Yu ; Yang, Yuan ; Zhou, Yun ; Zhang, Beibei ; Lu, Daru ; Wang, Hongyang ; Qian, Ji ; Jin, Li. / Common genetic variations of the cytochrome P450 1A1 gene and risk of hepatocellular carcinoma in a Chinese population. In: European Journal of Cancer. 2009 ; Vol. 45, No. 7. pp. 1239-1247.
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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.",
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AU - Shugart, Yin Yao

AU - Zhou, Weiping

AU - An, Yu

AU - Yang, Yuan

AU - Zhou, Yun

AU - Zhang, Beibei

AU - Lu, Daru

AU - Wang, Hongyang

AU - Qian, Ji

AU - Jin, Li

PY - 2009/5

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N2 - 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.

AB - 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.

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