MDR1 gene polymorphisms and risk of recurrence in patients with hepatocellular carcinoma after liver transplantation

Background and Objectives: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains a major cause of post-LT death. However, currently there is still lacking the markers to reliably predict recurrence. This study was undertaken to evaluate the association between three polymorphisms (C1236T, G2677A/T, C3435T) of Multidrug resistance 1 (MDR1) gene and the risk of recurrence after LT. Methods: Genomic DNA of 99 HCC patients undergoing LT was extracted from peripheral blood lymphocytes and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assay. Cox proportional hazard model was used to estimate the hazard ratios associated with polymorphisms. Results: During a mean follow-up of 14.9 months, 49 patients experienced recurrence. The association between recurrence-free and 2677A carrier (carrying at least one variant A allele) was significant (P = 0.019). However, no significant association was observed in other polymorphisms. Patients with 2677A carrier conferred a 63% reduction in recurrence risk compared with 2677A non-carrier (odds ratio: 0.374; 95% confidence interval: 0.177-0.788; P = 0.010). The median recurrence-free survival for 2677A carrier group was significantly longer than that for 2677A non-carrier group (44.2 vs. 10.5 months, P = 0.015). Conclusion: The polymorphism of MDR1 gene may be a valuable molecular marker for HCC recurrence after LT.