Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance).
Pharmacogenomics J
; 14(4): 336-42, 2014 Aug.
Article
in En
| MEDLINE
| ID: mdl-24513692
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sensory Receptor Cells
/
Axons
/
Breast Neoplasms
/
Paclitaxel
/
Peripheral Nervous System Diseases
/
Multifactorial Inheritance
/
Antineoplastic Agents, Phytogenic
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Pharmacogenomics J
Year:
2014
Document type:
Article