Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance).

Journal Article

Peripheral neuropathy is a common dose-limiting toxicity for patients treated with paclitaxel. For most individuals, there are no known risk factors that predispose patients to the adverse event, and pathogenesis for paclitaxel-induced peripheral neuropathy is unknown. Determining whether there is a heritable component to paclitaxel-induced peripheral neuropathy would be valuable in guiding clinical decisions and may provide insight into treatment of and mechanisms for the toxicity. Using genotype and patient information from the paclitaxel arm of CALGB 40101 (Alliance), a phase III clinical trial evaluating adjuvant therapies for breast cancer in women, we estimated the variance in maximum grade and dose at first instance of sensory peripheral neuropathy. Our results suggest that paclitaxel-induced neuropathy has a heritable component, driven in part by genes involved in axon outgrowth. Disruption of axon outgrowth may be one of the mechanisms by which paclitaxel treatment results in sensory peripheral neuropathy in susceptible patients.

Full Text

Duke Authors

Cited Authors

  • Chhibber, A; Mefford, J; Stahl, EA; Pendergrass, SA; Baldwin, RM; Owzar, K; Li, M; Winer, EP; Hudis, CA; Zembutsu, H; Kubo, M; Nakamura, Y; McLeod, HL; Ratain, MJ; Shulman, LN; Ritchie, MD; Plenge, RM; Witte, JS; Kroetz, DL

Published Date

  • August 2014

Published In

Volume / Issue

  • 14 / 4

Start / End Page

  • 336 - 342

PubMed ID

  • 24513692

Electronic International Standard Serial Number (EISSN)

  • 1473-1150

International Standard Serial Number (ISSN)

  • 1470-269X

Digital Object Identifier (DOI)

  • 10.1038/tpj.2014.2

Language

  • eng