Serum vitamin D deficiency and vitamin D receptor gene polymorphism as risk factors for hepatitis C virus related hepatocellular carcinoma

Abstract

Background:  Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver. In Egypt, there is a doubling in the incidence rate in the past 10 years. The screening of HCC still relies on the serum alpha-fetoprotein (AFP) level, which is ineffective in detecting small tumors. Therefore, novel and reliable diagnostic biomarkers associated with increased risk of HCC would better define high-risk populations, helping to improve prevention and treatment strategies. Vitamin D is a steroid hormone implicated in inhibition of carcinogenesis. Genetic variations in the vitamin D receptor (VDR) gene have been reported to associate with increased risk of cancers including breast, prostate, colorectal and liver cancers. The aim of this study is to evaluate the role of serum vitamin D level and VDR single nucleotide polymorphism (SNP) as predictors of hepatocellular carcinoma risk in the Egyptian hepatitis C virus (HCV) patients.

Methods: Venous blood samples were collected from 60 patients and 30 healthy subjects Patients were categorized into 2 groups: 30 patients with HCV-related HCC, and 30 patients with HCV-related cirrhosis without HCC. Serum levels of AFP and 25-OH D3 were measured using enzyme-linked immunosorbent assay (ELISA). DNA was extracted from whole blood and genotyping for VDR rs2228570 gene polymorphism was done using real time PCR, TaqMan assay.

Results: There was a significant decrease in the mean serum vitamin D level in HCC patients compared to non HCC cirrhotic patients and healthy subjects. VDR rs2228570 GG genotype was associated with a significant increased HCV-related HCC risk.

Conclusion: Low serum vitamin D level and VDR rs2228570 polymorphism may contribute to increased susceptibility to HCV-related HCC.