Increased DNA damage in hepatitis C virus-related hepatocellular carcinoma

DNA Cell Biol. 2014 Dec;33(12):884-90. doi: 10.1089/dna.2014.2417.

Abstract

One consequence of hepatitis C virus (HCV) infection is an elevated cancer risk. During chronic viral infection, deoxyribonucleic acid (DNA) damage is being induced by reactive oxygen and nitrogen species, which may play a pathogenic role in HCV-induced carcinogenesis. The study investigated DNA damage in peripheral blood lymphocytes from patients with hepatocellular carcinoma (HCC) and those with HCV infection with and without associated cirrhosis and normal controls. As a measure for genomic damage, the comet assay (single cell gel electrophoresis) was applied, which detects single- and double-strand breaks and alkali-labile sites through electrophoretic mobility of the resulting fragments. The levels of DNA damage were significantly higher in HCC and HCV-associated cirrhosis compared to HCV without cirrhosis and the control group. Patients presenting with DNA damage more than mean+two standard deviation of the controls had a 3.6-fold risk of having HCC more than those with undamaged DNA. HCV disease progression was the only discriminator predicting the extent of DNA damage. The accumulation of DNA damage is important in HCC evolution. DNA damage indicating intracellular oxidative and nitrative stress may lead to mutagenesis and consequently malignant transformation, which emphasizes the need to optimize the therapy for reducing the degree of genomic damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Case-Control Studies
  • DNA Damage*
  • Female
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Leukocytes, Mononuclear / pathology
  • Leukocytes, Mononuclear / virology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • ROC Curve
  • Young Adult