XRCC1 rs25487 genetic variant and TP53 mutation at codon 249 predict clinical outcomes of hepatitis B virus-related hepatocellular carcinoma after hepatectomy: A cohort study for 10 years' follow up

Hepatol Res. 2016 Jul;46(8):765-74. doi: 10.1111/hepr.12611. Epub 2015 Nov 12.

Abstract

Aim: To investigate the effects of rs25487 (the DNA repair gene: x-ray repair complementing defective repair in Chinese hamster cells 1 [XRCC1]) and codon 249 mutation (TP53 gene) on clinical outcomes of post-hepatectomy hepatitis B virus (HBV)-related HCC.

Methods: The XRCC1 rs25487 polymorphism and TP53 mutation at codon 249 of 485 hepatitis B surface antigen positive patients subjected to hepatectomy were genotyped via direct sequencing. SPSS software version 16.0 (SPSS, Chicago, IL, USA) was used to calculate survival of HCC patients according to primary end-points.

Results: The presence of at least one A allele (AA/AG) of rs25487 was associated with unfavorable prognosis (P = 0.005). Moreover, A allele (AA/AG) carriers were significantly associated with high risk of vascular invasion (P = 0.025) and regional invasion (P = 0.005). Differences were not significant between mutant and wild-type TP53 cases with overall survival (adjusted P = 0.400). Among the 485 participants, patients (n = 73) carrying both the A allele (AA/AG) of rs25487 and 249Ser TP53 mutation displayed decreased overall survival, compared with patients (n = 184) with the GG genotype of rs25487 and wild-type codon 249 (adjusted P = 0.007).

Conclusion: Polymorphisms of rs25487 may play a potential role in survival of HBV-related hepatocellular carcinoma patients following hepatectomy. While mutation at codon 249 of TP53 is not associated with HBV-related HCC survival in this study.

Keywords: codon 249; hepatitis B virus; hepatocellular carcinoma; prognosis; rs25487.