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

Pharmacogenomics J
Authors
Keywords
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.

Year of Publication
2014
Journal
Pharmacogenomics J
Volume
14
Issue
4
Pages
336-42
Date Published
2014 Aug
ISSN
1473-1150
URL
DOI
10.1038/tpj.2014.2
PubMed ID
24513692
PubMed Central ID
PMC4111770
Links
Grant list
U01 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