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

Background: Telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Telomere length is maintained by telomerase in 90% of human cancers,while 10% of cancers use an alternative mechanism of telomere lengthening termed (ALT).Another mechanism for Cancer cells is through activating or upregulating the normally silent human TERT gene (hTERT) that encodes telomerase Objectives:The aim of the present study wasto assess the role of telomeric length in the development of hepatocellular carcinoma(HCC) and to study the effect of 2SNPs in TERT gene rs13167280, rs2736098 on telomere length Subjects and Methods: the study was conducted on a total number of 100 patients,subdivided into two groups HCC and HCV groups.telomeric length was measured using quantitative real time PCR(sybergreen),SNP were measuring using Taqman probe on step{u2013}one real time PCRResults:We found thatthe patients with HCC had a significant short relative telomere length(RTL)with median level 0.15 compared to the median of HCV group which was 1.03 with the p-value <0.001.The performance of Relative telomere length was detected using ROC Curve. At the cut-off value of 0.7, RTL showed sensitivity 92 %, specificity 94%, diagnostic accuracy 93% and the area under the curve (AUC) were 0.917, and there was no statistical significant difference observed on comparing the two SNPs in HCC and HCV groups Conclusions: the median value of RTL in HCC patients was short compared to HCV patients, so the relative telomeric length could be used as a non invasive biomarker for HCC

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