Association of MnSOD Ala16Val genotype and activity with hepatocellular carcinoma risk in HCV-infected Egyptian patients

Background and study aims

Hepatocellular carcinoma (HCC) is the most common primary malignant tumour of the liver. Chronic infection with hepatitis C virus (HCV) is a risk factor for HCC occurrence. HCV infection causes oxidative stress in hepatic cells through overproduction of reactive oxygen species (ROS) that cause carcinogenesis. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that quenches free radicals. Ala16Val MnSOD polymorphism has been associated with cancer. It results from substitution of T to C at nucleotide 47 causing a change of valine to alanine on the 16th residue of 24-amino acid of mitochondrial-targeting sequence (MTS) of MnSOD.

This work aimed to assess the relationship between MnSOD Ala16Val genotype and activity and HCC development in HCV-infected Egyptian patients.

Patients and methods

This study was conducted on 75 HCV-infected HCC patients, 24 asymptomatic HCV-infected patients and 58 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis. MnSOD activity was measured using a superoxide dismutase assay kit.

Results

The HCC group included 56 males and 19 females. The mean±standard deviation (SD) of their age was 53.3±1.85 years. The Ala/Ala genotype frequency in HCC patients (36.0%) was significantly higher than that in asymptomatic HCV-infected patients (12.5%, p=0.029) and in the healthy controls (18.9%, p=0.031). There was a significant difference between MnSOD activity in HCC patients and those in asymptomatic HCV-infected patients and healthy controls (p=0.000). Moreover, there was a highly significant increase in MnSOD activity in HCC patients with Ala/Ala and Val/Ala than in those with Val/Val genotypes (p=0.007).

Conclusion

There is an evidence of association between Ala16Val MnSOD polymorphism and HCC occurrence in HCV-infected Egyptian patients. Furthermore, serum MnSOD activity was significantly higher in those patients compared to control subjects.