Abstract

Background: Small percentage of hepatitis C (HCV) patients develop hepatocellular carcinoma (HCC) during their lifetime, suggesting that genetic factors might modulate HCC development. Numerous variations on the vitamin D receptor gene (VDR) have been recognized in human cancers. The majority of them cause VDR to be unable to bind to 1, 25-OH-D. The aim of the present work was to investigate the relation of VDR FokI (rs2228570), BsmI (rs3782905) and ApaI (rs7975232) gene polymorphisms and the risk of HCC development in chronic HCV Egyptian patients. Methods: A total of 311 Egyptian patients were enrolled for this study. They were divided into 3 groups: 103 patients with liver Cirrhosis, 107 patients with HCC and 101 normal healthy subjects as the control group. Human genomic DNA Extraction was carried out using QIAamp® DNA Blood Mini Kit (QIAGEN) Genotyping of VDR ApaI (rs7975232) single nucleotide polymorphism (SNP) was carried out using real-time PCR TaqMan allelic discrimination assay with allele-specific designed fluorescent MGB probes. Results: Patients with HCC had a higher frequency of ApaI CC genotype (P=0.035) CI (0.031-0.038). Patients with HCC carried a higher ratio of ApaI CC genotype compared to those with liver cirrhosis (x2=5.4 and P = 0.03) or controls (x2=6.8 and P = 0.01). Univariate analysis revealed that age, lower platelet count (<150×103/μL), higher AFP (>100 ng/ml), and ApaI CC genotype were the factors significantly associated with the development of HCC. Stepwise logistic regression analysis showed that all were independent predictors. Conclusion: ApaI CC VDR gene mutation is an independent risk factor for HCC development in Egyptian Cirrhotic HCV patients.

Highlights

  • Hepatocellular carcinoma (HCC) is a major worldwide malignancy

  • Chronic hepatitis C virus (HCV) infection is characterized by a high rate of progression to fibrosis, chronic hepatitis, and eventually cirrhosis and to hepatocellular carcinoma (HCC) [2]

  • Total 311 participants of Egyptian origin were enrolled in this study. They were divided into 3 groups: 103 patients with HCV liver Cirrhosis, 107 patients with HCV related HCC and 101 normal healthy subjects as a control group

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Summary

Introduction

Hepatocellular carcinoma (HCC) is a major worldwide malignancy. Hepatocarcinogenesis is a complex process of variable etiologies mainly secondary to viral hepatitis infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) [1].Egypt suffers the highest prevalence of HCV infection, overwhelming their local health services. Hepatocellular carcinoma (HCC) is a major worldwide malignancy. Hepatocarcinogenesis is a complex process of variable etiologies mainly secondary to viral hepatitis infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) [1]. Chronic HCV infection is characterized by a high rate of progression to fibrosis, chronic hepatitis, and eventually cirrhosis and to HCC [2]. There is a continued need for the identification of hepatocarcinogenesis genetic risk factors for early identification and preventative interventions [3]. Small percentage of hepatitis C (HCV) patients develop hepatocellular carcinoma (HCC) during their lifetime, suggesting that genetic factors might modulate HCC development. The aim of the present work was to investigate the relation of VDR FokI (rs2228570), BsmI (rs3782905) and ApaI (rs7975232) gene polymorphisms and the risk of HCC development in chronic HCV Egyptian patients

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