Urinary 8-hydroxydeoxyguanosine in relation to XRCC1 rs25487 G/A (Arg399Gln) and OGG1 rs1052133 C/G (Ser326Cys) DNA repair genes polymorphisms in patients with chronic hepatitis C and related hepatocellular carcinoma

Cancer Manag Res. 2019 Jun 10;11:5343-5351. doi: 10.2147/CMAR.S209112. eCollection 2019.

Abstract

Background and aim: DNA repair represents a protective mechanism against cell injury and cancer. 8-hydroxy-deoxyguanosine (8-OHdG) is the main ROS-induced DNA mutation. The current study aimed to evaluate urinary 8-OHdG levels in patients with chronic hepatitis C virus (HCV) and its related hepatocellular (HCC) and correlate its level to XRCC1 rs25487 G/A and OGG1 rs1052133 C/G gene polymorphisms. Materials and methods: Urinary 8-OHdG assays were performed using HPLC technique, and XRCC1 rs25487 G/A and OGG1 rs1052133 C/G gene polymorphisms were analyzed by PCR using confronting two-pair primer method (PCR-CTPP) in 200 subjects allocated into 50 chronic HCV patients, 50 HCV-related HCC patients, and 100 controls. Results: There were significantly increased urinary 8-OHdG levels in HCV-related HCC and chronic HCV patients when compared with the controls (P<0.05 for all). Urinary 8-OHdG was associated with the tumor spread. Regarding, XRCC1 (Arg399Gln), AA (Gln/Gln) genotype and A-allele were more frequent in HCC and chronic HCV patients than in the controls (P<0.05). ORs (95%CI) using the dominant and the recessive genetic models were; 2.1 (1.1-4.1), P=0.032 and 1.9 (1-3.6), P=0.043 respectively. For OGG1 (Ser326Cys), GG (Cys/Cys) genotype and G-allele were increased significantly in chronic HCV and HCC patients compared to the controls (P<0.05). ORs (95%CI) under the dominant and the recessive genetic models were; 2.1 (1.1-4.1), P=0.032 and 1.9 (1-3.8), P=0.049 respectively. Additionally, XRCC1 (AA) and OGG1 (GG) genotypes had significantly increased urinary 8-OHdG levels among patients (P<0.05). Conclusions: XRCC1 (AA) and OGG1 (GG) could be considered as possible genotypic risk factors for HCV- related HCC development which were associated with significantly high urinary 8-hydroxy-deoxyguanosine levels, thus urinary 8-OHdG could be considered as non-invasive marker in follow-up chronic HCV progression into HCC.

Keywords: DNA repair; XRCC1 and OGG1 SNPs; confronting two-pair primers; hepatocellular carcinoma; high performance liquid chromatography; urinary 8-hydroxy-deoxyguanosine.