Molecular aspects of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors w orldwide. The major risk factors for HCC development are now well defined a nd some of the multiple steps involved in hepatocarcinogenesis have been el ucidated in recent years. However, no clear picture of how and in what sequ ence these factors interact at the molecular level has emerged yet. Maligna nt transformation of hepatocytes may occur as a consequence of various etio logies, such as chronic viral hepatitis, alcohol, and metabolic disorders, in the context of increased cellular turnover induced by chronic liver inju ry, regeneration and cirrhosis. Activation of cellular oncogenes, inactivat ion of tumor suppressor genes, overexpression of certain growth factors, an d possibly telomerase activation and DNA mismatch repair defects may contri bute to the development of HCC. Finally, aflatoxins have been shown to indu ce specific mutations of the p53 tumor suppressor gene, thus pointing to th e contribution of environmental factors to tumor development at the molecul ar level.