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

J Surg Oncol. 2007 Jul 1;96(1):62-8. doi: 10.1002/jso.20774.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adolescent
  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / surgery
  • Female
  • Genes, MDR*
  • Genotype
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / surgery
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Molecular Biology
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / genetics
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Risk

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1