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.

Comparative Studies on Tumor Protein 53 Gene Polymorphism, Demographic Attributes and Associated Risk Factors Among Hepatocellular Carcinoma and Liver Cirrhosis Patients in Calabar, Nigeria

“…The genotype and allelic frequency conformed to Hardy-Weinberg equilibrium principle, meaning that the evolutionary forces like mutation, genetic drift, selection, were not acting on the loci under consideration. This nding is similar to the documented research in Egypt(Zaky et al, (2020) where the genotypic and allelic frequency signi cantly conformed to Hardy-Weinberg equilibrium principle. The GT (Heterozygous mutations) and TT (Homozygous mutations) are causal alleles in our studied populations and are associated in the molecular etiology of liver cirrhosis in Calabar, Nigeria, similar to other published results in Ibadan, Nigeria [65], Egyptians populations[53.64] and Kenya[59, 68].…”

“…Jos [41,43], Egypt [21,42], Kenya [43,44], Iran [45,46] and other populations [47,48,49]. In contrast, more females having this disease were documented in Port-Harcourt [48,49] which are not in agreement with this current nding in Calabar.…”

“…When tumor suppressor genes do not function properly, cells can grow out of control, which will lead to cancer. According to [21] it is important for cells in multicellular organisms to suppress cancer. TP53 has been described as the guardian of the genome, which refers to its role in conserving stability by preventing genome mutation.…”

Analysis of the regulation of the mdm 2-p53 pathway by MiRNA-370-3P in hepatocellular carcinoma

“…In recent years, its incidence has been increasing rapidly in many major regions of the world, and it is also the second leading cause of tumor death in the world [1,2] . The early occurrence of liver cancer lesions can be inherited by the internal environment many factors such as basic and body epigenetic genetic conditions interact directly, and the development of chronic toxic hepatitis, alcohol consumption, long-term exposure to aflatoxin and genetic metabolic diseases are the risk factors that promote the occurrence of liver cancer [3] . In recent years, although our country liver cancer clinical early diagnosis and early treatment of patients, surgery and perioperative patient care technology improved, and part of the late primary liver cancer targeted therapy and the use of biological immunotherapy drugs, improve the majority of patients with clinical survival time, but still because of the current high incidence of liver cancer disease, high surgical recurrence rate and relatively limited drug treatment strategy, its future overall survival rate is still relatively not ideal [4] .…”