Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Hepatocellular carcinoma is the most common primary tumor of the liver. The molecular determinants of the HCC progression are still under investigations. TRAIL receptor 1 plays a very important role in many types of cancers including HCC. Genetic polymorphisms of TRAIL DR4, can modulate death signal transduction, which is important in induction of apoptosis and cause increase in the tumor progression. The aim of the present study was to investigate the effect of the DR4 polymorphisms C626G (Thr209Arg, rs20575) and A638C (Glu228Ala, rs20576) on the occurrence of hepatocellular carcinoma in Egyptian patients chronically infected with HCV. Genotyping of the candidate genes was performed by real time PCR assay in 80 HCC patients on top of HCV infection, and 80 HCV patients. The frequency distribution of rs20575 genotypes showed a statistically significant difference between the two studied groups (p = 0.020), the carriers of the C allele were 2.01 times more likely to develop HCC than the carriers of the G allele (p = 0.003), while no significant difference in rs20576 genotypes distribution was found between the studied groups (p = 0.680). On combining the carriers of C allele of rs20575 and the carriers of A allele of rs20576, a significant difference was detected (p > 0.001) with 2,85 higher risk of HCC development in patients who carried both genetic risk alleles simultaneously

Issued also as CD