Genetic Polymorphism of Selected Genes as Susceptible Risk Factors in the Progression of Hepatitis C Viral Infection to Hepatocellular Carcinoma

Abstract

Background: Owing to the high infection prevalence of hepatitis C virus (HCV), hepatocellular carcinoma (HCC) is considered a major health problem in Egypt. Identification of host genetic factors influencing the risk of developing HCC in patients with HCV infection may help to refine patients’ selection to benefit from specific preventative measures and/or adapted screening policies. Thus, the current study aimed to investigate the association of MTHFR C677T and A1298C in addition to TS 3´-UTR 1494del/ins 6bp polymorphisms with the susceptibility to HCV-related HCC in an Egyptian population. Method: Genotyping of the polymorphisms under study was performed using polymerase chain reaction-restriction fragment length polymorphism in 90 HCV-related HCC patients, 104 HCV-cirrhotic patients, and 100 healthy controls. Results: In healthy controls, the MTHFR C677T polymorphism under the homozygous codominant, recessive, and allelic models, the MTHFR A1298C polymorphism under all the genetic models, and TS polymorphism under the allelic model only were associated with an increased risk of HCC. In HCV patients, the MTHFR C677T polymorphism under all the genetic models, as well as both MTHFR A1298C and TS polymorphisms under the homozygous codominant model only, increased the susceptibility to HCC. The C/C and T/C haplotype combinations of MTHFR C677T and MTHFR A1298C polymorphisms conferred increased the risk for healthy subjects to develop HCC whereas, the T/C haplotype only contributed to increased susceptibility to HCC in HCV patients. Conclusion: MTHFR C677T and A1298C in addition to TS 3´-UTR 1494del/ins 6bp polymorphisms may contribute to the development of HCV-related HCC in an Egyptian population. These findings may aid in the early diagnosis and management of HCC.