Hepatitis B virus-induced oncogenesis.
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world with an annual incidence of more than 500000 in the year 2000. Its incidence is rising in many countries. Recently, it has been estimated that about 53% of HCC cases in the world are related to hepatitis B virus (HBV). The epidemiological association of HBV with HCC is well established. In recent studies, it was revealed that HBsAg carriers have a 25-37 times increased risk of developing HCC as compared to non-infected people. At present, HBV-associated carcinogenesis can be seen as a multi-factorial process that includes both direct and indirect mechanisms that might act synergistically. The integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion. The integration has been shown in a number of cases to affect a variety of cancer-related genes and to exert insertional mutagenesis. The permanent liver inflammation, induced by the immune response, resulting in a degeneration and regeneration process confers to the accumulation of critical mutations in the host genome. In addition to this, the regulatory proteins HBx and the PreS2 activators that can be encoded by the integrate exert a tumor promoter-like function resulting in positive selection of cells producing a functional regulatory protein. Gene expression profiling and proteomic techniques may help to characterize the molecular mechanisms driving HBV-associated carcinogenesis, and thus potentially identify new strategies in diagnosis and therapy.
Lupberger
Joachim
J
University of Freiburg, Department of Internal Medicine II, Hugstetter Strasse 55, Freiburg D-79106, Germany.
Hildt
Eberhard
E
D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000473:pathology / Q000821:virology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004279:DNA, Viral / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006509:Hepatitis B / Q000150:complications; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000502:physiology; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology / Q000821:virology*; D009154:Mutation / Q000235:genetics; D009858:Oncogenic Viruses / Q000235:genetics / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology; D012307:Risk Factors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000502:physiology
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C050807:presurface protein 2, hepatitis B surface antigen