You are here

Pharmacogenomics J DOI:10.1038/tpj.2014.2

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

Publication TypeJournal Article
Year of Publication2014
AuthorsChhibber, 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
JournalPharmacogenomics J
Volume14
Issue4
Pages336-42
Date Published2014 Aug
ISSN1473-1150
KeywordsAntineoplastic Agents, Phytogenic, Axons, Breast Neoplasms, Female, Humans, Multifactorial Inheritance, Paclitaxel, Peripheral Nervous System Diseases, Polymorphism, Single Nucleotide, Sensory Receptor Cells
Abstract

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.

URLhttp://dx.doi.org/10.1038/tpj.2014.2
DOI10.1038/tpj.2014.2
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24513692?dopt=Abstract

Alternate JournalPharmacogenomics J.
PubMed ID24513692
PubMed Central IDPMC4111770
Grant ListU01 GM61390 / GM / NIGMS NIH HHS / United States
U01 GM061393 / GM / NIGMS NIH HHS / United States
U10 CA031946 / CA / NCI NIH HHS / United States
U19 HL065962 / HL / NHLBI NIH HHS / United States
U10 CA033601 / CA / NCI NIH HHS / United States
U01 HL065962 / HL / NHLBI NIH HHS / United States
U01 GM61393 / GM / NIGMS NIH HHS / United States
U01 GM061390 / GM / NIGMS NIH HHS / United States
U19 GM061390 / GM / NIGMS NIH HHS / United States
P30 CA014236 / CA / NCI NIH HHS / United States
U10 CA180838 / CA / NCI NIH HHS / United States
T32 GM007175 / GM / NIGMS NIH HHS / United States
CA31946 / CA / NCI NIH HHS / United States