Journal Article

Temporal acquisition of sequential mutations in the enhancer II and basal core promoter of HBV in individuals at high risk for hepatocellular carcinoma

Xin Bai, Yu Zhu, Yan Jin, Xia Guo, Gengsun Qian, Taoyang Chen, Jing Zhang, Jinbing Wang, John D. Groopman, Jianren Gu and Hong Tu

in Carcinogenesis

Volume 32, issue 1, pages 63-68
Published in print January 2011 | ISSN: 0143-3334
Published online September 2010 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgq195
Temporal acquisition of sequential mutations in the enhancer II and basal core promoter of HBV in individuals at high risk for hepatocellular carcinoma

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To investigate the roles of mutations in enhancer II (Enh II) and basal core promoter (BCP) of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC), we determined the sequence of Enh II/BCP in 152 HCC and 136 non-HCC patients from a high-incidence area of East China. A longitudinal study was conducted on 21 cases in which serial plasma samples were available before HCC. In total, six point mutations, including T1653, V1753, T1762, A1764, T1766 and A1768, were found to occur more frequently in HCC patients. Multivariate analysis showed that the T1653 [odds ratio (OR), 2.07; 95% confidence interval (CI), 1.114–3.845] and V1753 (OR, 3.099; 95% CI, 1.520–6.317) were independent factors that were associated with HCC. Although a T1762/A1764 double mutation was found in 73.0% of the HCC patients and 66.9% of the non-HCC patients, if the combined pattern with other adjacent mutations was not taken into account, it alone showed a lower frequency in HCC patients compared with non-HCC patients (19.7 versus 34.6%, P = 0.005). Interestingly, while the OR of HCC patients with a double mutation was only 0.393 (95% CI, 0.234–0.660), it increased to 1.861 (95% CI, 1.161–2.984) with a triple mutation and to 4.434 (95% CI, 1.630–12.063) with a quadruple mutation. The longitudinal study demonstrated that the mutations in Enh II/BCP accumulated during the development of HCC. In conclusion, the T1653 and V1753 mutations were independent risk factors for HCC in East China. The T1762/A1764 double mutation was necessary but not sufficient to produce an association between Enh II/BCP mutations and HCC.

Journal Article.  4941 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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