Human TP53 gene polymorphisms among patients with hepatocellular carcinoma and chronic hepatitis B in Kenya

Abstract

Background: Human TP53 is the gatekeeper for generation of human cells and is highly conserved. Any alteration/mutation to TP53 adversely affects the regulatory function of the protein, potentially resulting in cancer. This study investigated mutations in codons 7 and 249 of TP53, among patients with hepatocellular carcinoma (HCC) and chronic hepatitis B virus (HBV) infection at the Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya. Methods: In total, 33 HBV-positive patients attending MTRH hospital between September 2013 and July 2017 were purposely selected from medical records for the study; those with HCC were confirmed from the cancer registry. The patients were aged between 25-67 years, with a male-to-female ratio of 1.1:1. Blood samples were collected from the patients. DNA was extracted, amplified and sequenced using TP53 forward and reverse primers. Gene mutation detection and analysis was done on exons 4 and 7 Results:  Of the 33 patients, 75.8% were chronically infected with HBV and had HCC; the rest were HBsAg positive without HCC. Homozygous proline was prevalent (54.5%) at exon 4 codon 72, followed by heterozygous Arg/Pro (33.3%) and lastly homozygous Arg/Arg (12.1%,). Pro/Pro allele was frequent in HCC group while Arg/Arg allele was common in patients without HCC. There was no significant association between the HCC and codon polymorphisms (p=0.12).  In exon 7, codon 249, 24.2% of patients had an Arg-Ser mutation of which, 75.0% had HCC and 25.0% did not. There was no significant association between HCC patients and codon 249 mutation (p=0.15). Conclusion: TP53 is a gene gate keeper, the mutations under study may dependently play a role in HCC development. This study did not find any association or clear mutational pattern between P53 mutations and HCC development. Therefore, TP53 mutation is a poor indicator for prognosis and a tumor’s biological behavior among HBV-positive subjects in Kenya.