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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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http://journal.hep.com.cn/fmd/EN/10.1007/s11684-010-0160-0
http://journal.hep.com.cn/fmd/EN/Y2010/V4/I4/419
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Wen-Ying LU
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