The correlation of hepatitis B virus pre-S mutation with cellular oxidative DNA damage in hepatocellular carcinoma

Hepatogastroenterology. 2008 Nov-Dec;55(88):2028-32.

Abstract

Background/aims: Recent research has proposed a role for HBV pre-S mutation in the development of HCC. Although the mechanism is not clear, pre-S mutant-induced endoplasmic reticulum (ER) stress and oxidative DNA damage may participate in this process. Therefore, we investigated the correlation of HBV pre-S mutation with ER stress and cellular oxidative DNA damage in HBV-related HCC patients.

Methodology: Thirty HBV-related HCC patients and 8 control patients were included. HBV DNA was extracted from sera and the HBV S coding region was analyzed by PCR and sequencing. Immunohistochemical staining for 8-oxoG and OGG1 were performed in HCC and non-neoplastic tissues.

Results: Study subjects were categorized into three groups: the pre-S mutant HBV-infected HCC patients (group 1, n=20), wild-type HBV-infected HCC patients (group 2, n=10) and HBV non-infected patients (group 3, n=8). The expression level of 8-oxoG and OGG1 in non-neoplastic tissue was higher in group 1/2 than in group 3; however, there was no significant difference between group 1 and 2. There was no significant difference in 8-oxoG/OGG1 expressions between HCC and non-neoplastic tissues.

Conclusions: The present study did not support a pathophysiologic role for HBV pre-S mutation, related to ER stress and oxidative DNA damage, in hepatocarcinogenesis.

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • DNA Damage / genetics*
  • DNA Glycosylases / metabolism
  • Endoplasmic Reticulum
  • Female
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B virus / genetics*
  • Humans
  • Immunohistochemistry
  • Liver / virology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Mutation / genetics
  • Oxidative Stress / genetics*
  • Protein Precursors / genetics*
  • Viral Envelope Proteins / genetics*

Substances

  • Hepatitis B Surface Antigens
  • Protein Precursors
  • Viral Envelope Proteins
  • presurface protein 1, hepatitis B surface antigen
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human