الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 164 |  |  |
| | | from | 164 | | |
Abstract
Hepatocellular carcinoma is one of the most frequently diagnosed cancers worldwide. HCV, HBV, aflatoxin B1, alcohol and non-alcoholic steatohepatitis are the most common causes of HCC. Egypt has the highest HCV prevalence worldwide which is an important leading cause of liver carcinogenesis.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 chronic hepatitis, fibrosis leading to cirrhosis, and ultimately to hepatocellular carcinoma (HCC).In addition to environmental factors, the accumulation of genetic changes was also demonstrated to play an essential role in liver carcinogenesis. Several genome wide association studies highlighted the possible role of genetic variants as significant determinants of HCC susceptibility.UDP glucuronosyltransferase 1A enzymes (UGT1A) catalyze the reaction of glucuronidation, which is one of the most important conjugative pathways for detoxification of several endogenous and exogenous compounds that could have a toxic or protective effect towards the liver injury induced by HCC risk factors.UGT1A locus encodes nine functional enzymes that differ in the first exons and their associated promoter regions that give the substrate specificity.Several single nucleotide polymorphisms have been described in the UGT1A gene in association with neoplastic and non-neoplastic diseases. In particular UGT1A polymorphisms have been related to, although with conflicting observations, cancers of the breast, prostate, colon-rectum and leukemia. UGT1A polymorphisms have been investigated in the context of some chronic liver diseases, such as viral hepatitis and alcoholic hepatitis.The aim of our study was to evaluate the association between UGT1A polymorphisms, SNP (rs4124874) and SNP (rs6742078), and susceptibility to HCC development in post-HCV cirrhosis.Ninety-one Egyptian patients, with post-HCV cirrhosis, were included in this study, and were divided into 2 groups:group Ι: HCC-free patients (n= 41) included 25 males and 16 females with a mean age of 58 ± 9 years group ΙΙ: HCC-positive patients (n= 50) included 40 males and 10 females with a mean age of 60 ± 7 years This study provided additional evidence of the contribution of UGT1A gene to susceptibility for HCC development in post-HCV cirrhosis. UGT1A (rs6742078) G/T polymorphism may be linked to susceptibility for HCC development in Egyptian individuals as the wild G allele, in recessive model, might decrease the risk of HCC development on top of HCV-induced cirrhosis. There was significant association between UGT1A (rs6742078) G/T polymorphism and the role of HCV infection in development of HCC. No significant association was found between UGT1A (rs4124874) G/T polymorphism and development of HCC. Further research studies on UGT1A gene polymorphism may help the better understanding of the pathogenesis of HCC on top of HCV-induced cirrhosis.