Epidermal growth factor (EGF) gene polymorphism as a risk factor for development of hepatocellular carcinoma (HCC) in chronic liver disease patients

Abstract

Hepatocellular carcinoma (HCC) accounts for 6% of all cancers worldwide. It is the fifth most common malignancy, with an estimated half million new cases diagnosed per year globally, and a mortality rate equivalent to its incidence. Despite major efforts to improve diagnosis and treatment of HCC, therapeutic options remain limited. The main therapeutic strategies are surgical resection of the tumor or liver transplantation. Although palliative treatments are needed, they remain very limited. Efforts to establish efficient systemic chemotherapy regimens have not succeeded and Best Supportive Care is still considered standard of treatment. Thus, the need for novel therapeutic agents and strategies is obvious. Lately, genomic targets and networks have increasingly gained attention due to the efforts of the Human Genome Project. As a result, human and many other genomic sequences are publicly available. This vast amount of newly available genomic data provides a rich source to identify novel genomic targets for therapeutic intervention. EGF gene polymorphism is associated with different types of tumors. This polymorphism is located in the 5-_untranslated region of the EGF gene. It consists of a substitution of guanine (G) for adenine (A) that leads to increased EGF expression by cultured peripheral-blood mononuclear cells. EGF results in cellular proliferation, differentiation, and survival. EGF up-regulations are a characteristic of cirrhotic liver disease.