Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients

Masashi Tatsukawa, Akinobu Takaki, Hidenori Shiraha, Kazuko Koike, Yoshiaki Iwasaki, Haruhiko Kobashi, Shin Ichi Fujioka, Kohsaku Sakaguchi, Kazuhide Yamamoto

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22 Citations (Scopus)

Abstract

Background: Hepatitis B virus (HBV) is a major cause of hepatocarcinogenesis.To identify mutations relevant to hepatocellular carcinoma (HCC) development, we compared the full genome sequences of HBV from the sera of patients with and without HCC.Methods: We compared the full genome sequences of HBV isolates from 37 HCC patients (HCC group 1) and 38 patients without HCC (non-HCC group 1). We also investigated part of the core promoter region sequences from 40 HCC patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who initially did not have HCC, 52 patients remained HCC-free during the follow-up period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC group 2). Serum samples collected from patients were subjected to PCR, and the HBV DNA was directly sequenced.Results: All patients had genotype C. A comparison of the nucleotide sequences of the HBV genome between HCC group 1 and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations in the core promoter region was significantly higher in the HCC group. These mutations tended to occur simultaneously in HCC patients. Multivariate analysis with group 2 revealed that the presence of HCC was associated with aging and the double mutation. Future emergence of HCC was associated with aging and the presence of a single G1613A mutation.Conclusions: G1613A and C1653T double mutations were frequently found in patients with HCC. A single G1613A mutation was associated with future emergence of HCC. These mutations may serve as useful markers in predicting HCC development.

Original languageEnglish
Article number458
JournalBMC Cancer
Volume11
DOIs
Publication statusPublished - Oct 21 2011

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Hepatitis B virus
Hepatocellular Carcinoma
Genotype
Mutation
Genome
Carcinoma
Genetic Promoter Regions
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients. / Tatsukawa, Masashi; Takaki, Akinobu; Shiraha, Hidenori; Koike, Kazuko; Iwasaki, Yoshiaki; Kobashi, Haruhiko; Fujioka, Shin Ichi; Sakaguchi, Kohsaku; Yamamoto, Kazuhide.

In: BMC Cancer, Vol. 11, 458, 21.10.2011.

Research output: Contribution to journalArticle

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abstract = "Background: Hepatitis B virus (HBV) is a major cause of hepatocarcinogenesis.To identify mutations relevant to hepatocellular carcinoma (HCC) development, we compared the full genome sequences of HBV from the sera of patients with and without HCC.Methods: We compared the full genome sequences of HBV isolates from 37 HCC patients (HCC group 1) and 38 patients without HCC (non-HCC group 1). We also investigated part of the core promoter region sequences from 40 HCC patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who initially did not have HCC, 52 patients remained HCC-free during the follow-up period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC group 2). Serum samples collected from patients were subjected to PCR, and the HBV DNA was directly sequenced.Results: All patients had genotype C. A comparison of the nucleotide sequences of the HBV genome between HCC group 1 and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations in the core promoter region was significantly higher in the HCC group. These mutations tended to occur simultaneously in HCC patients. Multivariate analysis with group 2 revealed that the presence of HCC was associated with aging and the double mutation. Future emergence of HCC was associated with aging and the presence of a single G1613A mutation.Conclusions: G1613A and C1653T double mutations were frequently found in patients with HCC. A single G1613A mutation was associated with future emergence of HCC. These mutations may serve as useful markers in predicting HCC development.",
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AU - Takaki, Akinobu

AU - Shiraha, Hidenori

AU - Koike, Kazuko

AU - Iwasaki, Yoshiaki

AU - Kobashi, Haruhiko

AU - Fujioka, Shin Ichi

AU - Sakaguchi, Kohsaku

AU - Yamamoto, Kazuhide

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