Impact of hepatitis virus and aging on DNA methylation in human hepatocarcinogenesis

Hepatocellular carcinoma (HCC) usually develops on the basis of chronic hepatitis and liver cirrhosis, where inactivation of several tumor suppressor genes (TSGs) takes place via methylation of the promoter. Interestingly, these methylation events are more prevalent in a background liver at high risk of HCC than one at low risk. Abnormal methylation is also observed in precancerous nodules such as dysplastic nodules and adenomas, suggesting that epigenetic alteration is an early event for HCC carcinogenesis. It is possible that infection with the hepatitis virus induces alteration of methylation at promoters of TSGs. Some studies suggested that viral proteins interfere with DNA methyltransferase in chronic hepatitis B. Induction of epigenetic alteration in chronic hepatitis C might, however, might be a consequence of oxidative stress. In addition, we proposed age should be taken into consideration for HCC development via epigenetic pathways. Further investigations are required to understand the mechanism of inducing epigenetic instability during hepatocarcinogenesis.