XRCC1 Gene Polymorphism Increases the Risk of Hepatocellular Carcinoma in Egyptian Population.

Mary Naguib,Eman Abdelsameea,Osama Hammam,Mohamed M Helwa,Ashraf M Eljaky,Mohamed Abdel-Samiee,Mohammed M Soliman,Hassan Zaghla

doi:10.31557/apjcp.2020.21.4.1031

Abstract

Section TitleSeveral major risk factors for hepatocellular carcinoma (HCC) have been identified, including chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Nevertheless, only a fraction of infected patients develops HCC during their lifetime suggesting that genetic factors might modulate HCC development. X-ray repair cross complementing group1 (XRCC1) participates in the repair pathways of DNA. Aim:to investigate the association between XRCC1 gene polymorphism and HCC in Egyptian chronic hepatitis C patients. Methods:This study was assessed on 40 patients with HCC secondary to chronic HCV infection who were compared to 20 cirrhotic HCV patients and 40- age and gender- matched healthy control group. After collection of relevant clinical data and basic laboratory tests, c.1517G>C SNP of XRCC1 gene polymorphism was performed by (PCR-RFLP) technique. Results:A statistically higher frequency of XRCC1 (CC, GC) genotypes and increased (C) allele frequency in patients with HCC was found in comparison to cirrhotic HCV patients as well as control group. In addition, patients with the XRCC1 (CC, GC) genotypes had significantly higher number and larger size of tumor foci and significantly higher Child Pugh grades. Multivariate analysis showed that the presence of c.1517G>C SNP of XRCC1 gene is an independent risk for the development of HCC in chronic HCV patients with 3.7 fold increased risk of HCC development. In conclusion: XRCC1 gene polymorphism could be associated with increased risk of HCC development in chronic HCV Egyptian patients.

Highlights

Hepatocellular carcinoma (HCC) is a worldwide health problem
This study was assessed on 40 patients with hepatocellular carcinoma (HCC) secondary to chronic hepatitis C virus (HCV) infection who were compared to 20 cirrhotic HCV patients and 40- age and gender- matched healthy control group
Multivariate analysis showed that the presence of c.1517G>C SNP of X-ray repair cross complementing group1 (XRCC1) gene is an independent risk for the development of HCC in chronic HCV patients with 3.7 fold increased risk of HCC development

Summary

Introduction

Hepatocellular carcinoma (HCC) is a worldwide health problem. In Egypt, it represents the second most common cancer in men and the sixth most common cancer in women (Omar et al, 2013). Hepatocellular carcinoma is the third cause of mortality due to cancer (El-Garawani et al, 2020). Several risk factors have been recognized, including chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) (Hasan et al, 2014). Chronic liver inflammation is associated with repair and tissue remodelling processes, which may lead to chromosomal damage and subsequent progression to cirrhosis and initiation of hepatocarcinogenesis (Gao et al, 2012). DNA is under constant threat from endogenous and exogenous DNA damaging agents. Conserved DNA repair systems are settled to process DNA damage and maintain genomic integrity (Abbotts et al, 2014). The X-ray repair cross-complementing group (XRCC1) which is responsible for repair of oxidative DNA damage and single-strand breaks (London, 2015)

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