Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance) Journal Article
| Authors: | Chhibber, A.; Mefford, J.; Stahl, E. A.; Pendergrass, S. A.; Baldwin, R. M.; Owzar, K.; Li, M.; Winer, E. P.; Hudis, C. A.; Zembutsu, H.; Kubo, M.; Nakamura, Y.; McLeod, H. L.; Ratain, M. J.; Shulman, L. N.; Ritchie, M. D.; Plenge, R. M.; Witte, J. S.; Kroetz, D. L. |
| Article Title: | Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance) |
| 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. © 2014 Macmillan Publishers Limited All rights reserved. |
| Keywords: | major clinical study; single nucleotide polymorphism; pathogenesis; paclitaxel; cancer adjuvant therapy; phenotype; multiple cycle treatment; sensory neuropathy; breast cancer; neuropathy; peripheral neuropathy; cohort analysis; genetic association; genetic variability; genotype; disease severity; patient information; genetic predisposition; heritability; pathway; phase 3 clinical trial (topic); inheritance; nerve fiber growth; polygenic; human; female; priority journal; article |
| Journal Title: | Pharmacogenomics Journal |
| Volume: | 14 |
| Issue: | 4 |
| ISSN: | 1470-269X |
| Publisher: | Springernature |
| Date Published: | 2014-08-01 |
| Start Page: | 336 |
| End Page: | 342 |
| Language: | English |
| DOI: | 10.1038/tpj.2014.2 |
| PROVIDER: | scopus |
| PMCID: | PMC4111770 |
| PUBMED: | 24513692 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2014 -- CODEN: PJHOA -- Source: Scopus |
