Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma

被引：23
作者：
Xie J.-X. [1 ]
Zhao J. [2 ]
Yin J.-H. [1 ]
Zhang Q. [1 ]
Pu R. [1 ]
Lu W.-Y. [1 ]
Zhang H.-W. [1 ]
Wang H.-Y. [3 ]
Cao G.-W. [1 ]
机构：
[1] Department of Epidemiology, Second Military Medical University
[2] Department of Hepatobiliary Surgery, the 3rd Affiliated Hospital, Second Military Medical University
[3] International Laboratory for Signal Transduction, the 3rd Affiliated Hospital, Second Military Medical University
来源：
Frontiers of Medicine in China | 2010年 / 4卷 / 4期
基金：
中国国家自然科学基金;
关键词：
genotype; haplotype; hepatitis B virus; hepatocellular carcinoma; mutation;
D O I：
10.1007/s11684-010-0160-0
中图分类号：
学科分类号：
摘要：
The association of viral mutations and haplotypic carriages with mutations in the preS region of hepatitis B virus (HBV) genotypes B and C with hepatocellular carcinoma (HCC) is of great significance for the prediction of this malignancy, but it remains obscure. We analyzed the preS sequences of HBV genotypes B and C from 1172 HBV-infected subjects including 231 patients with HCC. As compared with the HBV-infected subjects without HCC, C2875T, G2946C, A3054C, C3060A, T3066C, C3116T, A3120C, G3191A, A1C, C7A, C10A, A31C, C76T, G105C, and G147C in both genotypes were significantly associated with increased risks of HCC. C2875A, G2950A, G2951A, A3054T, C3060T, T3066A, T3069G, A3120T, and G3191C were significantly associated with increased risks of HCC in genotype C, whereas these mutations were inversely associated with HCC in genotype B. Multivariate regression analyses showed that C76A/T was a novel factor independently associated with an increased risk of HCC, as compared with those without HCC. The frequencies of haplotypes 2964A-3116T-preS2 start codon wild-type-7C, 2964C-3116T-7A-76C, and 2964A-3116T-7C-76A/T were significantly higher in the patients with HCC (P<0.001), whereas a haplotypic carriage with a single mutation and another three wildtypes were inversely associated with HCC. Conclusively, the association of HBV mutations in the preS region with HCC depends on HBV genotype and haplotypic carriage with two or more mutations that are each associated with an increased risk of HCC independently. © 2010 Higher Education Press and Springer-Verlag Berlin Heidelberg.
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页码：419 / 429
页数：10
相关论文
共 21 条
  • [1] Nguyen V.T., Law M.G., Dore G.J., Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden, J Viral Hepat, 16, 7, pp. 453-463, (2009)
  • [2] El-Serag H.B., Rudolph K.L., Hepatocellular carcinoma: epidemiology and molecular carcinogenesis, Gastroenterology, 132, 7, pp. 2557-2576, (2007)
  • [3] Yin J., Zhang H., Li C., Gao C., He Y., Zhai Y., Zhang P., Xu L., Tan X., Chen J., Cheng S., Schaefer S., Cao G., Role of hepatitis B virus genotype mixture, subgenotypes C2 and B2 on hepatocellular carcinoma: compared with chronic hepatitis B and asymptomatic carrier state in the same area, Carcinogenesis, 29, 9, pp. 1685-1691, (2008)
  • [4] Liu S., Zhang H., Gu C., Yin J., He Y., Xie J., Cao G., Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis, J Natl Cancer Inst, 101, 15, pp. 1066-1082, (2009)
  • [5] Cao G.W., Clinical relevance and public health significance of hepatitis B virus genomic variations, World J Gastroenterol, 15, 46, pp. 5761-5769, (2009)
  • [6] Yin J., Zhang H., He Y., Xie J., Liu S., Chang W., Tan X., Gu C., Lu W., Wang H., Bi S., Cui F., Liang X., Schaefer S., Cao G., Distribution and hepatocellular carcinoma-related viral properties of hepatitis B virus genotypes in Mainland China: a community-based study, Cancer Epidemiol Biomarkers Prev, 19, 3, pp. 777-786, (2010)
  • [7] Kay A., Zoulim F., Hepatitis B virus genetic variability and evolution, Virus Res, 127, 2, pp. 164-176, (2007)
  • [8] Chen B.F., Liu C.J., Jow G.M., Chen P.J., Kao J.H., Chen D.S., High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases, Gastroenterology, 130, 4, pp. 1153-1168, (2006)
  • [9] Gao Z.Y., Li T., Wang J., Du J.M., Li Y.J., Li J., Lu F.M., Zhuang H., Mutations in preS genes of genotype C hepatitis B virus in patients with chronic hepatitis B and hepatocellular carcinoma, J Gastroenterol, 42, 9, pp. 761-768, (2007)
  • [10] Cao Z., Bai X., Guo X., Jin Y., Qian G., Tu H., High prevalence of hepatitis B virus pre-S mutation and its association with hepatocellular carcinoma in Qidong, China, Arch Virol, 153, 10, pp. 1807-1812, (2008)
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