TP53 polymorphism as a risk factor for hepatocellular carcinoma in hepatitis C virus-infected Egyptian patients

• The association between the TP53 Arg72Pro polymorphism and the risk of HCC in HCV patients was studied.
• The relation between the TP53 Arg72Pro polymorphism and the plasma TP53 levels was also studied.
• The Pro/Pro genotype and the Pro allele of TP53 codon 72 are associated with increased risk of HCC.
• The plasma TP53 level is downregulated in HCC.

Background and aimsHuman hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Polymorphisms of the TP53 gene are known to play an important role in HCC. It is aimed to investigate the impact of the Arg72Pro polymorphism of TP53 in the development of HCC among chronic hepatitis C patients with different stages of liver disease.Subjects & methodsThis study included 69 HCC patients, 101 liver cirrhosis (LC) patients and 46 healthy, unrelated, age-matched volunteers as controls, from the same locality of Egypt. The HCC and LC patients were suffering from HCV infection. The Arg72Pro polymorphism of codon 72 was tested by PCR, followed by restriction enzyme digestion (PCR-RFLP).ResultsThe results showed that the Proline allele significantly increases the risk of HCC development (OR 2.461, 95% CI 1.391–4.3558, P = 0.002, Z* = 3.094), compared with the development of LC. The variant genotypes were also associated with the risk of HCC (Pro/Pro: OR 3.7956, 95% CI 1.9228–7.4923, P = 0.0001; Arg/Pro: OR 2.099, 95% CI 1.0911–4.0383, P = 0.0263; Arg/Arg: OR 1.9594, 95% CI 1.0023–3.8306, P = 0.0492). There was a significant decrease in the plasma TP53 level in the HCC group when compared with the LC group or with the control group (P = 0.000).ConclusionThis case–control analysis confirmed that the Pro/Pro (C/C) genotype and the Pro (C) allele of TP53 codon 72 are associated with increased risk of HCC in HCV-infected patients. Additionally, the data suggest that the plasma TP53 level is downregulated in HCC.