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

A. Chhibber, J. Mefford, E. A. Stahl, S. A. Pendergrass, R. M. Baldwin, K. Owzar, M. Li, E. P. Winer, C. A. Hudis, H. Zembutsu, M. Kubo, Y. Nakamura, H. L. McLeod, M. J. Ratain, L. N. Shulman, M. D. Ritchie, R. M. Plenge, J. S. Witte, D. L. Kroetz

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)336-342
Number of pages7
JournalPharmacogenomics Journal
Volume14
Issue number4
DOIs
Publication statusPublished - 08-2014

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Multifactorial Inheritance
Peripheral Nervous System Diseases
Paclitaxel
Genes
Phase III Clinical Trials
Neuronal Outgrowth
Therapeutics
Genotype
Breast Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Chhibber, A., Mefford, J., Stahl, E. A., Pendergrass, S. A., Baldwin, R. M., Owzar, K., ... Kroetz, D. L. (2014). Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance). Pharmacogenomics Journal, 14(4), 336-342. https://doi.org/10.1038/tpj.2014.2
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. / Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance). In: Pharmacogenomics Journal. 2014 ; Vol. 14, No. 4. pp. 336-342.
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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.",
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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 2014, 'Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance)', Pharmacogenomics Journal, vol. 14, no. 4, pp. 336-342. https://doi.org/10.1038/tpj.2014.2

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

In: Pharmacogenomics Journal, Vol. 14, No. 4, 08.2014, p. 336-342.

Research output: Contribution to journalArticle

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AU - Chhibber, A.

AU - Mefford, J.

AU - Stahl, E. A.

AU - Pendergrass, S. A.

AU - Baldwin, R. M.

AU - Owzar, K.

AU - Li, M.

AU - Winer, E. P.

AU - Hudis, C. A.

AU - Zembutsu, H.

AU - Kubo, M.

AU - Nakamura, Y.

AU - McLeod, H. L.

AU - Ratain, M. J.

AU - Shulman, L. N.

AU - Ritchie, M. D.

AU - Plenge, R. M.

AU - Witte, J. S.

AU - Kroetz, D. L.

PY - 2014/8

Y1 - 2014/8

N2 - 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.

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