Association between donor and recipient smoothened gene polymorphisms and the risk of hepatocellular carcinoma recurrence following orthotopic liver transplantation in a Han Chinese population

Abstract

Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) is potential cause for the poor outcome. Smoothened (SMO) gene has been considered associating with HCC and HCC recurrence, but its association with HCC recurrence after OLT is not clear yet. In this study, we aim at evaluating the association between donor and recipient SMO gene polymorphisms and HCC recurrence after OLT. A total of 76 patients with HCC who had undergone OLT from July 2007 to August 2012 were included. A single nucleotide polymorphism (SNP), SMO rs3824, located at the 3'UTR region, was genotyped and analyzed in both donor and recipient. We demonstrated that recipient rs3824 polymorphism was significantly associated with HCC recurrence following OLT. In multivariate logistic regression analysis, TNM stage (p = 0.001), recipient SMO rs3824 genotype (CG vs. CC/GG p = 0.001), and histologic grade (p = 0.019) were identified as independent risk factors of HCC recurrence. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the recipient CC/GG group than in the CG group (p = 0.003 and p = 0.011, respectively). Cox proportional hazards modeling revealed that TNM stage, recipient SMO rs3824 genotype, pre-OLT serum AFP level, and histologic grade were independent factors (p < 0.05) for patients' clinical outcomes. In conclusion, recipient SMO rs3824 polymorphism is associated with an increased risk of HCC recurrence following OLT and has a potential clinical value for the prognosis of HCC patients treated with OLT.

Keywords: Hepatocellular carcinoma; Orthotopic liver transplantation; Prognosis; Recurrence; SMO polymorphism.