The Role of the Vitamin D Receptor Gene Polymorphisms in Hepatocarcinogenesis

Hepatitis C virus (HCV) infection is one of the major public health problems worldwide . Chronic HCV infection is characterized by a high rate of progression to fibrosis, chronic hepatitis, leading to cirrhosis and ultimately to hepatocellular carcinoma (HCC). Early detection is critically important because the most effective treatment for HCC is surgical resection or ablation therapy when the tumour is small. On the other hand, genetic factors can also contribute, particularly gene polymorphisms of inflammatory cytokines and growth factor ligands and receptors . Vitamin D is involved in the metabolism of skeleton as a systemic hormone but also has important roles in the regulation of host immune responses, fibrogenesis and development of cancer through vitamin D receptor (VDR). Previous data have suggested that vitamin D levels may influence cancer development. In particular, several single nucleotide polymorphisms have been described in the VDR gene, and some polymorphisms are associated with tumor occurrence. For instance, VDR polymorphisms have been related to cancers of the breast, prostate, skin, colon-rectum, bladder and kidney, although with conflicting observations. VDR polymorphisms have also been investigated in the context of some chronic liver diseases, such as chronic hepatitis B, primary biliary cirrhosis and autoimmune hepatitis . In a recent published study, VDR polymorphism may be used as a molecular marker to predict the risk and to evaluate the disease severity of HCC in patients with chronic hepatitis B.

A significant association of VDR ApaI polymorphism with the development of HCC in chronic HCV infection may help to identify those who are at high risk of developing HCC.