Hepatocellular carcinoma: molecular biology of its growth and relationship to hepatitis B virus infection

Abstract

Hepatocellular carcinoma is a very common tumor worldwide and is associated with high mortality rates. Evidence that the development of hepatocellular carcinoma is related to chronic HBV infection has accumulated from epidemiologic studies, information from animal and cell culture models, and molecular biologic evidence that HBV components can be found within hepatocellular carcinoma tissue. Integration of HBV DNA within host liver cell chromosomes may be a crucial step in the development of hepatocellular carcinoma. Integration is associated with disruption of both structure and function of DNA at the site of integration. The study of individual examples of HBV DNA integration in hepatocellular carcinoma tissue illustrates possible mechanisms of hepatocarcinogenesis by HBV. In many cases, activation of various growth factors has been found in association with HBV DNA integration including IGF II, oncogenes such as c-myc, and novel growth factors such as the retinoic acid receptor. A clearer understanding of the mechanisms involved may allow for possible therapeutic interventions in the future, or perhaps even the prevention of hepatocellular carcinoma.