الفهرس 
IntroductionOnly 14 pages are availabe for public view
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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