Association between TP53 and MDM2 Gene Polymorphisms and Risk of Hepatocellular Carcinoma in Hepatitis C Virus among Egyptian Populations

Abstract

Background: The Murine double minute 2 (MDM2) gene is overexpressed in several human tumors. The oncogenic potential of MDM2 is partially explained by inhibition of the activity of the tumor suppressor protein P53 (negative regulator of the P53 tumor suppressor protein). A single nucleotide polymorphism (SNP) in the promoter region of MDM2 gene (T to G exchange at nucleotide 309) and TP53 gene (codon 72 exon 4, rs1042522 encoding either C or G) have been independently associated with increased risk of several cancer types. Few studies have analyzed the role of these polymorphisms in the development of hepatocellular carcinoma among Egyptian patients with chronic hepatitis C virus infection. Methods: The study consisted in the comparison of the genotype distribution of TP53 and MDM2 SNP309 in 100 viral hepatitis C-related hepatocellular carcinomas (HCC) cases and 100 controls without HCC matched for age, gender and ethnicity. PCR-RFLP (restriction fragment length polymorphism) and real time PCR methods were used to determine the genotype at the MDM2 SNP309T>G locus and TP53 rs1042522. Results: Overall, our results indicate that frequencies of TP53 alleles (C and G) were not significant different between HCC cases and healthy controls (p=0.093) (Odds Ratio, OR=1.361,95% Confidence Interval, 95% CI=0.949 – 1.951). A significant increase of MDM2 SNP309 G/G and T/G genotypes were observed among HCC cases (Odds Ratio, OR=4.868, 95% Confidence Interval, 95% CI= 2.873 – 8.251). Conclusions: Our finding suggest that people who have G allele increase the risk by 4.868 folds for developing HCC among Egyptian patients, consequently the MDM2 309T>G polymorphism is an important modulator of hepatocellular carcinoma development in Egyptian patients.