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Frontiers of Medicine

Front. Med.    2010, Vol. 4 Issue (4) : 419-429     DOI: 10.1007/s11684-010-0160-0
Research articles |
Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma
Jia-Xin XIE1,Jian-Hua YIN1,Qi ZHANG1,Rui PU1,Wen-Ying LU1,Hong-Wei ZHANG1,Guang-Wen CAO1,Jun ZHAO2,Hong-Yang WANG3,
1.Department of Epidemiology, Second Military Medical University, Shanghai 200433, China; 2.Department of Hepatobiliary Surgery, the 3rd Affiliated Hospital, Second Military Medical University, Shanghai 200433, China; 3.International Laboratory for Signal Transduction, the 3rd Affiliated Hospital, Second Military Medical University, Shanghai 200433, China;
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Abstract 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 wild-types 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.
Keywords hepatitis B virus      hepatocellular carcinoma      mutation      genotype      haplotype      
Issue Date: 05 December 2010
 Cite this article:   
Wen-Ying LU,Jia-Xin XIE,Qi ZHANG, et al. Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma[J]. Front. Med., 2010, 4(4): 419-429.
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Wen-Ying LU
Jia-Xin XIE
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PMID: 19302335
El-Serag H B, Rudolph K L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 2007, 132(7): 2557–2576
PMID: 17570226
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 hepatocellularcarcinoma: compared with chronic hepatitis B and asymptomatic carrierstate in the same area. Carcinogenesis, 2008, 29(9): 1685–1691
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Liu S, Zhang H, Gu C, Yin J, He Y, Xie J, Cao G. Associations between hepatitis B virusmutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst, 2009, 101(15): 1066–1082
PMID: 19574418
Cao G W. Clinical relevance and public health significance ofhepatitis B virus genomic variations. World J Gastroenterol, 2009, 15(46): 5761–5769
PMID: 19998495
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 hepatocellularcarcinoma-related viral properties of hepatitis B virus genotypesin Mainland China: a community-based study. Cancer Epidemiol Biomarkers Prev, 2010, 19(3): 777–786
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Kay A, Zoulim F. Hepatitis B virus genetic variability and evolution. Virus Res, 2007, 127(2): 164–176
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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 hepatitisB virus carriers with progressive liver diseases. Gastroenterology, 2006, 130(4): 1153–1168
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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 Chepatitis B virus in patients with chronic hepatitis B and hepatocellularcarcinoma. J Gastroenterol, 2007, 42(9): 761–768
PMID: 17876546
Cao Z, Bai X, Guo X, Jin Y, Qian G, Tu H. High prevalence of hepatitis B virus pre-S mutation andits association with hepatocellular carcinoma in Qidong, China. Arch Virol, 2008, 153(10): 1807–1812
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Fang Z L, Sabin C A, Dong B Q, Wei S C, Chen Q Y, Fang K X, Yang J Y, Huang J, Wang X Y, Harrison T J. Hepatitis B virus pre-S deletionmutations are a risk factor for hepatocellular carcinoma: a matchednested case-control study. J Gen Virol, 2008, 89(Pt 11): 2882–2890
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Yin J, Xie J, Zhang H, Shen Q, Han L, Lu W, Han Y, Li C, Ni W, Wang H, Cao G. Significant association of different preS mutations with hepatitis B-related cirrhosisor hepatocellular carcinoma. J Gastroenterol, 2010, 45(10): 1063–1071
PMID: 20419326
Chen J, Yin J, Tan X, Zhang H, Zhang H, Chen B, Chang W, Schaefer S, Cao G. Improved multiplex-PCR to identify hepatitis B virus genotypes A-F and subgenotypesB1, B2, C1 and C2. J Clin Virol, 2007, 38(3): 238–243
PMID: 17224304
Zhang H W, Yin J H, Li Y T, Li C Z, Ren H, Gu C Y, Wu H Y, Liang X S, Zhang P, Zhao J F, Tan X J, Lu W, Schaefer S, Cao G W. Risk factors for acute hepatitis B and its progression to chronichepatitis in Shanghai, China. Gut, 2008, 57(12): 1713–1720
PMID: 18755887
Shen T, Yan X M, Zou Y L, Gao J M, Dong H. Virologic characteristics of hepatitis B virus in patients infected via maternal-fetal transmission. World J Gastroenterol, 2008, 14(37): 5674–5682
PMID: 18837083
Bock C T, Tillmann H L, Maschek H J, Manns M P, Trautwein C. A preS mutation isolated from a patient with chronic hepatitis B infectionleads to virus retention and misassembly. Gastroenterology, 1997, 113(6): 1976–1982
PMID: 9394738
Hsieh Y H, Su I J, Wang H C, Chang W W, Lei H Y, Lai M D, Chang W T, Huang W. Pre-S mutant surface antigens in chronichepatitis B virus infection induce oxidative stress and DNA damage. Carcinogenesis, 2004, 25(10): 2023–2032
PMID: 15180947
Kekulé A S, Lauer U, Meyer M, Caselmann W H, Hofschneider P H, Koshy R. The preS2/S region of integratedhepatitis B virus DNA encodes a transcriptional transactivator. Nature, 1990, 343(6257): 457–461
PMID: 2153938
G?bel F, Taschner S, Jurkin J, Konradi S, Vaculik C, Richter S, Kneidinger D, Mühlbacher C, Bieglmayer C, Elbe-Bürger A, Strobl H. Reciprocal role of GATA-1 and vitamin D receptor in human myeloid dendritic celldifferentiation. Blood, 2009, 114(18): 3813–3821
PMID: 19721012
Andrieux L O, Fautrel A, Bessard A, Guillouzo A, Baffet G, Langou?t S. GATA-1 is essential in EGF-mediatedinduction of nucleotide excision repair activity and ERCC1 expressionthrough ERK2 in human hepatoma cells. Cancer Res, 2007, 67(5): 2114–2123
PMID: 17332341
Banerjee R, Caruccio L, Zhang Y J, McKercher S, Santella R M. Effects of carcinogen-induced transcription factors on the activationof hepatitis B virus expression in human hepatoblastoma HepG2 cellsand its implication on hepatocellular carcinomas. Hepatology, 2000, 32(2): 367–374
PMID: 10915744
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