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

Abstract

<ns3:p> Background Human <ns3:italic>TP53</ns3:italic> is the gatekeeper for generation of human cells and is highly conserved. Some alteration/mutation in <ns3:italic>TP53</ns3:italic> adversely affects the regulatory function of the protein, potentially resulting in cancer. This study investigated mutations in codons 72 and 249 of <ns3:italic>TP53</ns3:italic> , 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 <ns3:italic>TP53</ns3:italic> forward and reverse primers. Gene mutation detection and analysis was done on exons 4 codon 72 and exon 7 codon 249. 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 <ns3:italic>TP53</ns3:italic> is a gene gate keeper, the mutations under study may dependently play a role in HCC development. This study did not find any association between <ns3:italic>TP53</ns3:italic> mutations and presence of HCC. Therefore, <ns3:italic>TP53</ns3:italic> Arg-72 and Ser-249 mutation is not a clear prognosis indicator for hepatocellular carcinoma among HBV infected patients in Kenya. </ns3:p>