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Abstract
In sub-Saharan Africa and Asia, hepatocellular carcinoma (HCC) is a major cause of cancer death. The primary etiologic agents identified in these regions are chronic infection with hepatitis B virus (HBV) and dietary exposure to aflatoxin B1 (AFB1). Epidemiologic evidence and experimental evidence support the association of HBV and AFB1 with an increased risk of HCC and suggest that combined exposure may act synergistically.
Tumor suppressor protein P53 is a multifunctional transcription factor involved in the control of cell cycle progression, DNA integrity, and cell survival. Tumor-specific p53 mutations have been identified in several human cancers. A selective guanine-to-thymine transversion mutation in codon 249 leading to an arginine-to-serine substitution) of the P53 gene (also known as TP53) has been identified as a ”hotspot” mutation for HCC. Epidemiologic evidence and experimental evidence have suggested that in HCC this mutation is strongly associated with exposure to AFB1.
In the present study the aim of this work is the evaluation of 249 P53 mutation as a diagnostic marker for HCC.
This study was done between October 2006 and October 2007. The patients were choosen from the Tropical Medicine department, Ain Shams University and from the Gastroentrology Department, Kobry El Qoba Military Hospital.
The work included 60 patients and were classified into:
Group 1 (study group): Includes 30 patients with HCC, their age ranged from 41 to 70 years with a mean 53 years. 26 were males (86.67%) and 4 females (13.33%).
Group 2 (control group): Includes 30 patients with chronic liver disease, their aged ranged from 39 to 66 with a mean 56 years. 28 were males (93.33%) and 2 females (6.67%).
Each studied case was subjected to history taking, clinical examination, complete biochemical and virological study, abdominal US and CT, in addition to ser249 p53 gene mutation done by restriction endonuclease digestion of polymerase chain reaction products from exon 7.
In this study we found that there is a higher percentage of Ser 249 p53 mutation in plasma DNA among patients with hepatocellular carcinoma than among patients with chronic liver disease and this difference was found to be statistically significant .
We also found a statistically significant correlation between Ser-249 P53 mutation in plasma and the number of hepatic focal lesions .
Hepatitis markers where perfomed and revealed increased frequency of HCV infection in both groups. HCV infection in the chronic liver disease group were 80% and HBV were 40% , while in HCC group HCV were73.3 % and HBV were46.6% .
There is increased incidence of ser 249 p53 mutations among HCV patients with HCC but this result was statistically insignificant.
Also we did not observe any statistical differences in chronic infection with HBV between those patients with HCC who were positive for the Ser 249 P53 mutation in plasma DNA and patients with HCC who were negative for this mutation
The present study found that there is no significant correlation between the presence of ser 249 P53 mutations and the level of alpha-fetoprotein in HCC.
As regard the liver function tests, our data showed that there is no statistical difference between negative and positive ser 249 P53 mutation among patients with HCC as regards total bilirubin, AST, ALT, and albumin, also there is no statistical difference between negative and positive ser 249 P53 mutation among patients with HCC as regards ESR