Genetic variants of XRCC1 and risk of hepatocellular carcinoma in chronic hepatitis C patients

ABSTRACT

Background: Hepatitis C virus (HCV) related liver cirrhosis occurs in about 20% of chronically infected patients over a duration of 10–20 years, and within 5 years approximately 10–20% of these cirrhotic patients will develop hepatocellular carcinoma (HCC). Previous studies report that the X-ray repair cross-complementing group1 gene (XRCC1) is important in the risk of HCC development; however, results obtained from these studies are conflicting rather than conclusive. We hypothesised an association between single nucleotide polymorphisms (SNPs) in XRCC1 with the HCC risk on a background of chronic hepatitis C.

Materials and methods: We recruited 210 subjects, 70 with HCC, 70 with cirrhosis and 70 healthy controls. Two SNPs [c.1254C>T(rs2293035) and c.1517G>C(rs139599857)] in XRCC1 were genotyped using created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods.

Results: The TT genotype, CT genotype and T-allele in c.1254C>T (rs2293035) were linked to risk of HCC compared to the CC genotype: OR 3.58 [confidence interval (CI) 95%: 1.19–10.7] p = 0.019; OR 2.16 (CI 95%: 1.04–4.47) p = 0.037 and OR 2.10 (CI 95%: 1.2–3.3) p = 0.006, respectively. Regarding c.1517G>C (rs139599857), the CC genotype, GC genotype and C-allele were linked with higher risk of developing HCC compared to GG genotype: OR 4.77 (CI 95%: 1.3–16.9), p = 0.016; OR 3.02 (CI 95%: 1.46–6.2), p = 0.002 and OR 2.4 (CI 95%: 1.4–4.0), p = 0.001, respectively.

Conclusion: We conclude that the T-allele of c.1254C>T (rs2293035) and the C allele of c.1517G>C (rs139599857) genetic variants may be associated with increased HCC risk among chronic hepatitis C patients.

KEYWORDS:

• XRCC1 gene
• polymorphisms
• HCC
• HCV

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Informed consent

Written informed consent was obtained from patients who participated in this study.

Ethics committee approval

Ethics committee approval was received for this study from the Institutional Review Board of Mansoura Faculty of Medicine (Code number: MS/611; Decision Date: 17.06.2014).

Disclosure statement

No potential conflict of interest was reported by the authors.