The Role of the Vitamin D Receptor Gene Polymorphisms in Hepatocarcinogenesis

The Role of the Vitamin D Receptor Gene Polymorphisms in Hepatocarcinogenesis in Cirrhotic Patients Infected With Chronic Hepatitis C Virus

Previous data have suggested that vitamin D levels may influence cancer development. In particular, several single nucleotide polymorphisms have been described in the Vitamin D receptor( VDR gene), and some polymorphisms are associated with tumor occurrence. For instance, VDR polymorphisms have been related to cancers of the breast, prostate, skin, colon-rectum, bladder and kidney, although with conflicting observations . VDR polymorphisms have also been investigated in the context of some chronic liver diseases, such as chronic hepatitis B, primary biliary cirrhosis and autoimmune hepatitis . In a recent published study, VDR polymorphism may be used as a molecular marker to predict the risk and to evaluate the disease severity of HCC in patients with chronic hepatitis B.

A significant association of VDR (ApaI) polymorphism with the development of HCC in chronic HCV infection may help to identify those who are at high risk of developing HCC.

Study Overview

• Status: Unknown
• Conditions: Liver Cancer
• Intervention / Treatment: Other: The VDR genotype

Detailed Description

Hepatitis C virus (HCV) infection is one of the major public health problems worldwide . Chronic HCV infection is characterized by a high rate of progression to fibrosis, chronic hepatitis, leading to cirrhosis and ultimately to hepatocellular carcinoma (HCC). Early detection is critically important because the most effective treatment for HCC is surgical resection or ablation therapy when the tumour is small. On the other hand, genetic factors can also contribute, particularly gene polymorphisms of inflammatory cytokines and growth factor ligands and receptors . Vitamin D is involved in the metabolism of skeleton as a systemic hormone but also has important roles in the regulation of host immune responses, fibrogenesis and development of cancer through vitamin D receptor (VDR). Previous data have suggested that vitamin D levels may influence cancer development. In particular, several single nucleotide polymorphisms have been described in the VDR gene, and some polymorphisms are associated with tumor occurrence. For instance, VDR polymorphisms have been related to cancers of the breast, prostate, skin, colon-rectum, bladder and kidney, although with conflicting observations. VDR polymorphisms have also been investigated in the context of some chronic liver diseases, such as chronic hepatitis B, primary biliary cirrhosis and autoimmune hepatitis . In a recent published study, VDR polymorphism may be used as a molecular marker to predict the risk and to evaluate the disease severity of HCC in patients with chronic hepatitis B.

A significant association of VDR ApaI polymorphism with the development of HCC in chronic HCV infection may help to identify those who are at high risk of developing HCC.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Elgharbia
    • Tanta, Elgharbia, Egypt
      • Recruiting
      • Tanta university - faculty of medicine
      • Contact: Sherief Abdelsalam, lecturer; Phone Number: 00201095159522; Email: Sheriefabdelsalam@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hcv cirrhotic patient with and without Hcc

Exclusion Criteria:

• Malignancy other than HCC
• Co-infection with Hepatitis B virus (HBV) and Human immunodeficiency virus (HIV)
• Cirrhosis is due to causes other than chronic hepatitis C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Hepatocellular carcinoma (HCC); The VDR genotype in 20 HCV cirrhotic patient with HCC	Other: The VDR genotype; The VDR genotype will determined by polymerase chain reaction (PCR) amplication and restriction length fragment polymorphisms.
Other: Liver cirrhosis; The VDR genotype in 20 HCV cirrhotic patient without HCC	Other: The VDR genotype; The VDR genotype will determined by polymerase chain reaction (PCR) amplication and restriction length fragment polymorphisms.
Other: Control group; The The VDR genotype in 10 healthy individuals as control	Other: The VDR genotype; The VDR genotype will determined by polymerase chain reaction (PCR) amplication and restriction length fragment polymorphisms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
number of HCC patients with abnormal (APAL) VDR polymorphism	6 months

Collaborators and Investigators

• Sponsor: Sherief Abd-Elsalam
• Collaborators: Tanta University
• Investigators: Principal Investigator: Fathia Asal, Prof, hepatology dept-Tanta; Study Director: Amal El Bendary, Professor, Clinicalpathology dept-Tanta; Study Director: WALAA Elkhalawany, lecturer, hepatology dept-Tanta; Study Chair: Basma Shetaa, physician, Tanta University

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: May 31, 2015
• First Submitted That Met QC Criteria: May 31, 2015
• First Posted (Estimate): June 3, 2015

Study Record Updates

• Last Update Posted (Actual): January 3, 2018
• Last Update Submitted That Met QC Criteria: December 30, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: liver cancer

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No