New epidemiological data on liver oncogenesis.
The purpose of this review is to address and discuss the following: a) the malignant transformation of hepatocytes may occur, irrespective of the etiologic agent, in the context of increased cellular turnover induced by chronic hepatic damage and regeneration, with genetic mutations being a frequent event prior to the development of this tumor; b) although it is clear that hepatitis B virus-induced chronic liver injury, regeneration and cirrhosis is a major risk factor for hepatocellular carcinoma development, there are also several reports of the direct carcinogenic effects of hepatitis B virus. For instance, integration of hepatitis B virus DNA can directly induce chromosomal rearrangements and viral gene product transactivating properties may influence cellular genes important in the control of the growth process; c) hepatitis C virus and other risk agents, including alcohol, environmental factors and metabolic diseases may operate, mainly through chronic liver damage that progress to liver cirrhosis, a major predisposing factor for the development of hepatocellular carcinoma, regardless of etiology; d) at the molecular level, the interaction between oncogenes, tumor suppressor genes (with or without aflatoxins and hepatitis B virus) and several growth factors may play an additional role in hepatocellular carcinoma development.
Department of Medicine, Aristotelian University of Thessaloniki, Greece. jannis@med.auth.gr
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J
Kountouras
N J
NJ
Lygidakis
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D002471:Cell Transformation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D009857:Oncogenes / Q000502:physiology; D012307:Risk Factors