Comparison study on the complete sequence of hepatitis B virus identifies new mutations in core gene associated with hepatocellular carcinoma

Yu Zhu, Yan Jin, Xia Guo, Xin Bai, Taoyang Chen, Jinbing Wang, Gengsun Qian, John Davis Groopman, Jianren Gu, Jinjun Li, Hong Tu

Research output: Contribution to journalArticle

Abstract

Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC). Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls. Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W. Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC.

Original languageEnglish (US)
Pages (from-to)2623-2630
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number10
DOIs
StatePublished - Oct 2010

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Hepatitis B virus
Hepatocellular Carcinoma
Mutation
Genes
Genome
Carcinoma
Initiator Codon
Validation Studies
Point Mutation
Liver Diseases
China
Multivariate Analysis
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Comparison study on the complete sequence of hepatitis B virus identifies new mutations in core gene associated with hepatocellular carcinoma. / Zhu, Yu; Jin, Yan; Guo, Xia; Bai, Xin; Chen, Taoyang; Wang, Jinbing; Qian, Gengsun; Groopman, John Davis; Gu, Jianren; Li, Jinjun; Tu, Hong.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 19, No. 10, 10.2010, p. 2623-2630.

Research output: Contribution to journalArticle

Zhu, Yu ; Jin, Yan ; Guo, Xia ; Bai, Xin ; Chen, Taoyang ; Wang, Jinbing ; Qian, Gengsun ; Groopman, John Davis ; Gu, Jianren ; Li, Jinjun ; Tu, Hong. / Comparison study on the complete sequence of hepatitis B virus identifies new mutations in core gene associated with hepatocellular carcinoma. In: Cancer Epidemiology Biomarkers and Prevention. 2010 ; Vol. 19, No. 10. pp. 2623-2630.
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abstract = "Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC). Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls. Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95{\%} confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W. Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC.",
author = "Yu Zhu and Yan Jin and Xia Guo and Xin Bai and Taoyang Chen and Jinbing Wang and Gengsun Qian and Groopman, {John Davis} and Jianren Gu and Jinjun Li and Hong Tu",
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T1 - Comparison study on the complete sequence of hepatitis B virus identifies new mutations in core gene associated with hepatocellular carcinoma

AU - Zhu, Yu

AU - Jin, Yan

AU - Guo, Xia

AU - Bai, Xin

AU - Chen, Taoyang

AU - Wang, Jinbing

AU - Qian, Gengsun

AU - Groopman, John Davis

AU - Gu, Jianren

AU - Li, Jinjun

AU - Tu, Hong

PY - 2010/10

Y1 - 2010/10

N2 - Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC). Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls. Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W. Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC.

AB - Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC). Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls. Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W. Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC.

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