HBV mutations in EnhII/BCP/PC region contribute to the prognosis of hepatocellular carcinoma

Cancer Med. 2019 Jun;8(6):3086-3093. doi: 10.1002/cam4.2169. Epub 2019 Apr 29.

Abstract

Background: Accompanied by HBV infection, HBV mutations gradually occur because HBV polymerase appears proofread deficiencies. In our previous study, we have identified that EnhII/BCP/PC mutations and genotype C of HBV DNA were associated with hepatocellular carcinoma (HCC) risk. In this study, we extend our research to explore HCC prognosis associated genotype and mutations in EnhII/BCP/PC regions.

Methods: We designed a case-cohort study of 331 HCC patients to evaluate the effects of the HBV genotypes and mutations on HCC survival. Log-rank test and Cox proportional hazard models were used for the analyses.

Results: Results showed that genotype C, which was more frequent in HBV-related HCC (77.4%), presented a negative signal with HCC survival. Interestingly, we detected a significant association between EnhII/BCP/PC mutation nt1753 and HCC prognosis (Log-rank P = 0.034). Subgroup analysis revealed that this risk effect was more pronounced in non-B genotype (P = 0.090 for heterogeneity test). We also detected a borderline multiplicative interaction between genotypes of nt1753 and HBV genotype on HCC survival (P for interaction = 0.069).

Conclusions: These findings indicated that, in Chinese population, nt1753 in EnhII/BCP/PC region might be a novel marker for HCC prognosis.

Keywords: HBV genotype; HBV mutation; HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / complications*
  • Humans
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Promoter Regions, Genetic / genetics*