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Abstract Hepatocellular carcinoma (HCC) is the sixth most prevalent malignant tumour and the third leading cause of cancer related death worldwide, accounting for over half a million deaths per year. Chronic hepatitis B (HBV) and C (HCV) viral infections play a major role in the HCC aetiology. However, not all the individuals infected with HBV/HCV develop HCC, indicating implication of other environmental and genetic risk factors in the multistage process of this complex disease. In Egypt, the incidence rate of HCC has increased sharply in the last few years. This could be due to HBV, HCV epidemic infection. On the other hand improvements in diagnostic tools and health care led to increased survival rate among cirrhotic patients allowing time for some of them to develop HCC. T cells play an important role in antitumor immunity. The inability of lymphocytes to develop effective immune response to malignancy may be explained by the presence of suppressive factors in the tumour such as cytotoxic T-lymphocyte antigen-4 (CTLA-4), interleukins IL-10 and IL- 4, which prevent tumor infiltrating lymphocytes from transforming into effector cells. The cytotoxic T-lymphocyte antigen 4 is an inhibitory receptor expressed on the cell surface of activated memory T cells and CD4+ CD25+ regulatory T cells, leading to down regulation of cell-mediated immune responses. CTLA-4 gene, is located on chromosome 2q33, it is composed of four exons that encode separate functional domains; leader sequence, extracellular domain, trans membrane domain, and cytoplasmic domain. Recommendations The +49 A/G (rs231775) SNP at 1st exon, of CTLA-4 gene has been linked to auto immune diseases and/or cancer development. It has been suggested that such SNPs would enhance the receptor-legand interaction, hence augmenting its inhibitory effect on T cell. The association between CTLA-4 gene polymorphism and certain types of cancers had been reported by several researchers such asCozar et al., 2007; Wang et al., 2007. However, little is known about the relationship between genetic polymorphisms in CTLA-4 and susceptibility to liver diseases, except that the +49 A/G (rs231775) SNP was found to be associated with virus B persistence, hence influencing |