title: Paclitaxel-induced neuropathy: potential association of MAPT and GSK3B genotypes.
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-3β (GSK3β) 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.
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.forename: John B
authors.initials: JB
authors.lastname: Kwok
authors.forename: Clement T
authors.initials: CT
authors.lastname: Loy
authors.forename: Michael L
authors.initials: ML
authors.lastname: Friedlander
authors.forename: Cindy S-Y
authors.initials: CS
authors.lastname: Lin
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
authors.forename: Craig R
authors.initials: CR
authors.lastname: Lewis
authors.affiliation: Brain and Mind Research Institute, University of Sydney, Sydney, Australia. matthew.kiernan@sydney.edu.au.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D017239:Paclitaxel / Q000009:adverse effects* / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000209:etiology*; D011110:Polymorphism, Genetic; D016875:tau Proteins / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C054369:MAPT protein, human; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D017239:Paclitaxel