SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02507882

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide as well as in Egypt. Despite improvements in HCC therapy, the prognosis for HCC patients remains poor. Today molecular, genomic and epigenomic aberrations in tumors are being deeply investigated. Many biomarkers were associated to HCC onset, and they could be useful for clinicians, but all show some limitations and no one is so early to predict the HCC onset. It is estimated that 51.5% of HCC cases can be attributed to HCV infection. Moreover, there is a large occult reservoir of HCV caused chronic liver disease in approximately 9 % in the Egyptian with estimated 6 million HCV chronic infections and estimated 150 000 new infections per year. Among them, we have to mention the polymorphism of IL28B gene rs12979860 C/T. and rs 4803217. The IL-28B gene encodes interferon-lambda 3 (IFN-λ3), which belongs to the type III IFN family. IFN-λ interacts with a transmembrane receptor inducing a potent antiviral response. In experimental model of HCV type III IFN was able to inhibit viral replication. IL-28B polymorphisms are linked to the efficiency of the inflammatory process during HCV infection, and to the mechanisms that HCV adopts to escape by innate and adaptive immunity. During the last years, a number of studies have assessed the association between the IL-28B polymorphisms and risk of HCC and liver cirrhosis (LC) occurrence in various populations; however, results obtained are still inconclusive. Interestingly, some polymorphisms located at the 3' untranslated region (UTR) of IL28B, e.g. rs 4803217, seem to interfere with the binding of miRNA, to date recognized as important post-transcriptional regulators. In the last years miRNAs acquired a growing relevance as potential biomarkers for several diseases including cancer, and many researches are focusing on understanding their role in cancer. Thus the objectives of the current proposal are to determine through investigating a cohort of 405 patients, whether IL28B rs12979860 and rs4803217 polymorphisms are associated to the risk of HCC in chronic hepatitis C (CHC) patients and, above all, to identify their role as predictor marker of HCC in CHC, when associated to miRNAs modulation. Data obtained by our work could be helpful in HCC diagnosis, thus leading to the improvement of the patients prognosis. The proposed activities are going to be implemented through a partnership us as Egyptian Liver Research Institute and Hospital (ELRIAH)- Dakhlya- Egypt and Non- Egyptian Partners.

NCT02507882 HCV Infection ( Genotype 4)
MeSH: Carcinoma, Hepatocellular
HPO: Hepatocellular carcinoma

2 Interventions

Name: IL28B Polymorphism

Description: SNP rs12979860 and 4803217 will be determined in whole blood by allelic discrimination using specific probes by real time PCR.

Type: Biological

HCC HCC with Cirrhosis HCV related HCC patients

Name: miRNA quantification

Description: RNAs will be extracted from serum using miRNeasy Mini Kit (Quiagen) according to the manufacturer's instruction. The RNA purity will be assessed by the RNA concentration and quantified by NanoDrop ND-1000 (Nanodrop, United States). cDNA will be obtained by miScript II Reverse Transcription Kits (Quiagen) A Preamplification will be performed using miScript PreAMP PCR Kits (Quiagen) Real Time PCRarray will be done using miScript miRNA PCR Arrays, with SYBR Green PCR Master Mix (Quiagen).

Type: Biological

HCC HCC with Cirrhosis HCV related HCC patients


Primary Outcomes

Description: Different types of IL28B and their relation to the progressiveness of HCC

Measure: IL-28B rs12979860 and rs4803217 Genotype evaluation

Time: 6 months to 1 year from the start of the study

Measure: Specific miRNA levels and their association with degree of fibrosis, cirrhosis and HCC

Time: 1 to 2 years from the start of the study

Purpose: Prevention

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 rs12979860

Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma.

Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide as well as in Egypt.

Among them, we have to mention the polymorphism of IL28B gene rs12979860 C/T. and rs 4803217.

Thus the objectives of the current proposal are to determine through investigating a cohort of 405 patients, whether IL28B rs12979860 and rs4803217 polymorphisms are associated to the risk of HCC in chronic hepatitis C (CHC) patients and, above all, to identify their role as predictor marker of HCC in CHC, when associated to miRNAs modulation.

IL-28B rs12979860 and rs4803217 Genotype evaluation.

rs12979860 C/T and rs4803217.

Objectives The overall goal is to investigate the Impact of IL-28B rs12979860 and rs4803217 gene polymorphisms associated with miRNAs deregulation on HCV-related hepatocellular carcinoma Specific Objectives: 1.

3. IL28B Polymorphism: SNP rs12979860 and 4803217 will be determined in whole blood by allelic discrimination using specific probes by real time PCR.

IL28B SNPs comparisons will be done by stratifying patients according to rs12979860CC and rs12979860CT/TT genotypes and 4803217 Analysis miRNA PCR Array will be done by specific Data Analysis Software specifically supplied by Quiagen.


2 rs4803217

Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma.

Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide as well as in Egypt.

Thus the objectives of the current proposal are to determine through investigating a cohort of 405 patients, whether IL28B rs12979860 and rs4803217 polymorphisms are associated to the risk of HCC in chronic hepatitis C (CHC) patients and, above all, to identify their role as predictor marker of HCC in CHC, when associated to miRNAs modulation.

IL-28B rs12979860 and rs4803217 Genotype evaluation.

rs12979860 C/T and rs4803217.

Objectives The overall goal is to investigate the Impact of IL-28B rs12979860 and rs4803217 gene polymorphisms associated with miRNAs deregulation on HCV-related hepatocellular carcinoma Specific Objectives: 1.



HPO Nodes


HPO:
Hepatocellular carcinoma
Genes 54
PMS1 HFE KRAS MST1 FAH IL12A TGFBR2 MET IL12RB1 MSH6 RASGRP1 TCF4 BMPR1A SERPINA1 PMS2 MLH3 IGF2 IGF2R MMEL1 ATP7B SPIB PDGFRL PIK3CA GPR35 SLC25A13 JAG1 AHCY APC MLH1 TJP2 ABCB11 CASP8 HMBS POU2AF1 CASP10 PRKCD IRF5 RPS20 MSH2 SEMA4A CTNNB1 SPRTN UROD FAS FASLG EPCAM G6PC TNFSF15 SLC37A4 TNPO3 H19 TP53 AXIN1 FAN1