Paclitaxel-induced neuropathy: potential association of MAPT and GSK3B genotypes

Susanna B. Park, John B. Kwok, Clement T. Loy, Michael L. Friedlander, Cindy S. Y. Lin, Arun V. Krishnan, Craig R. Lewis, Matthew C. Kiernan*

*Corresponding author for this work

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Abstract

Background: Paclitaxel treatment produces dose-limiting peripheral neurotoxicity, which adversely affects treatment and long-term outcomes. In the present study, the contribution of genetic polymorphisms to paclitaxel-induced neurotoxicity were assessed in 21 patients, focusing on polymorphisms involved in the tau-microtubule pathway, an important target of paclitaxel involved in neurotoxicity development. Methods: Polymorphisms in the microtubule-associated protein tau (MAPT) gene (haplotype 1 and rs242557 polymorphism) and the glycogen synthase kinase-3ß (GSK3ß) gene (rs6438552 polymorphism) were investigated. Neurotoxicity was assessed using neuropathy grading scales, neurophysiological studies and patient questionnaires. Results: A significant relationship between the GSK-3B rs6438552 polymorphism and paclitaxel-induced neurotoxicity was evident. Conclusions: Polymorphisms in tau-associated genes may contribute to the development of paclitaxel-induced neurotoxicity, although larger series will be necessary to confirm these findings.

Original languageEnglish
Article number993
Pages (from-to)1-5
Number of pages5
JournalBMC Cancer
Volume14
Issue number1
DOIs
Publication statusPublished - 22 Dec 2014
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2014. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • GSK3ß
  • MAPT
  • Neuropathy
  • Neurotoxicity
  • Paclitaxel

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