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Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China.
Pharmacogenet Genomics. 2006 Mar; 16(3):219-27.PG

Abstract

OBJECTIVES

Aflatoxin B1 exposure is one of the major risk factors for hepatocellular carcinoma (HCC). CYP1A2 is a cytochrome P450 isoenzyme that plays an important role in the bioactivation of AFB1 to its carcinogenic metabolite. The study was designed to assess whether genetic polymorphisms in CYP1A2 are associated with HCC susceptibility in a high-risk region.

METHODS

A case-control study of 431 HCC cases and 550 cancer-free controls recruited from an HCC endemic region in China was carried out. Three single nucleotide polymorphisms, namely -3860G > A (CYP1A2*1C), -3113G > A, and 5347T > C (CYP1A2*1B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism methods.

RESULTS

Homozygous carriers of the major haplotype -3860G/-3113G/5347C were associated with increased HCC susceptibility in the overall population (odds ratio [OR] = 1.65, 95% confidence interval [CI]: 1.11-2.46, P = 0.014), in HBsAg seronegative individuals (OR = 2.69, 95% CI: 1.43-5.06, P = 0.002), and in heavy smokers (OR = 2.14, 95% CI: 1.21-3.80, P=0.009). In addition, individuals carrying at least one CYP1A2*1C allele showed significantly decreased HCC risk (OR = 0.49, 95% CI: Q0.27-0.86, P = 0.013) in the HBsAg seronegative subpopulation. Furthermore, as compared with HBsAg seropositive patients, wild-type homozygotes of the CYP1A2*1C polymorphism were significantly over-represented in HBsAg seronegative patients (P = 0.024). No significant association between CYP1A2 genetic polymorphisms and HCC risk was observed in either HBsAg seropositive individuals or non-smokers.

CONCLUSIONS

CYP1A2 genetic polymorphisms are associated with HCC susceptibility in smokers and HBsAg seronegative individuals in the Fusui endemic region.

Authors+Show Affiliations

Department of Genomics & Proteomics, Beijing Institute of Radiation Medicine, Beijing, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16495781

Citation

Chen, Xiaoping, et al. "Association of CYP1A2 Genetic Polymorphisms With Hepatocellular Carcinoma Susceptibility: a Case-control Study in a High-risk Region of China." Pharmacogenetics and Genomics, vol. 16, no. 3, 2006, pp. 219-27.
Chen X, Wang H, Xie W, et al. Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China. Pharmacogenet Genomics. 2006;16(3):219-27.
Chen, X., Wang, H., Xie, W., Liang, R., Wei, Z., Zhi, L., Zhang, X., Hao, B., Zhong, S., Zhou, G., Zhang, L., Gao, X., Zhu, Y., & He, F. (2006). Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China. Pharmacogenetics and Genomics, 16(3), 219-27.
Chen X, et al. Association of CYP1A2 Genetic Polymorphisms With Hepatocellular Carcinoma Susceptibility: a Case-control Study in a High-risk Region of China. Pharmacogenet Genomics. 2006;16(3):219-27. PubMed PMID: 16495781.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China. AU - Chen,Xiaoping, AU - Wang,Haijian, AU - Xie,Weimin, AU - Liang,Renxiang, AU - Wei,Zhongliang, AU - Zhi,Lianteng, AU - Zhang,Xiumei, AU - Hao,Bingtao, AU - Zhong,Shaofei, AU - Zhou,Gangqiao, AU - Zhang,Lingqiang, AU - Gao,Xue, AU - Zhu,Yunping, AU - He,Fuchu, PY - 2006/2/24/pubmed PY - 2006/8/1/medline PY - 2006/2/24/entrez SP - 219 EP - 27 JF - Pharmacogenetics and genomics JO - Pharmacogenet Genomics VL - 16 IS - 3 N2 - OBJECTIVES: Aflatoxin B1 exposure is one of the major risk factors for hepatocellular carcinoma (HCC). CYP1A2 is a cytochrome P450 isoenzyme that plays an important role in the bioactivation of AFB1 to its carcinogenic metabolite. The study was designed to assess whether genetic polymorphisms in CYP1A2 are associated with HCC susceptibility in a high-risk region. METHODS: A case-control study of 431 HCC cases and 550 cancer-free controls recruited from an HCC endemic region in China was carried out. Three single nucleotide polymorphisms, namely -3860G > A (CYP1A2*1C), -3113G > A, and 5347T > C (CYP1A2*1B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Homozygous carriers of the major haplotype -3860G/-3113G/5347C were associated with increased HCC susceptibility in the overall population (odds ratio [OR] = 1.65, 95% confidence interval [CI]: 1.11-2.46, P = 0.014), in HBsAg seronegative individuals (OR = 2.69, 95% CI: 1.43-5.06, P = 0.002), and in heavy smokers (OR = 2.14, 95% CI: 1.21-3.80, P=0.009). In addition, individuals carrying at least one CYP1A2*1C allele showed significantly decreased HCC risk (OR = 0.49, 95% CI: Q0.27-0.86, P = 0.013) in the HBsAg seronegative subpopulation. Furthermore, as compared with HBsAg seropositive patients, wild-type homozygotes of the CYP1A2*1C polymorphism were significantly over-represented in HBsAg seronegative patients (P = 0.024). No significant association between CYP1A2 genetic polymorphisms and HCC risk was observed in either HBsAg seropositive individuals or non-smokers. CONCLUSIONS: CYP1A2 genetic polymorphisms are associated with HCC susceptibility in smokers and HBsAg seronegative individuals in the Fusui endemic region. SN - 1744-6872 UR - https://www.unboundmedicine.com/medline/citation/16495781/Association_of_CYP1A2_genetic_polymorphisms_with_hepatocellular_carcinoma_susceptibility:_a_case_control_study_in_a_high_risk_region_of_China_ L2 - https://doi.org/10.1097/01.fpc.0000194424.20393.c6 DB - PRIME DP - Unbound Medicine ER -