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

被引：31

作者：

Chhibber, A. ^{[1
,2
,3
]}

Mefford, J. ^{[3
,4
]}

Stahl, E. A. ^{[5
,6
]}

Pendergrass, S. A. ^{[7
]}

Baldwin, R. M. ^{[1
,2
,3
]}

Owzar, K. ^{[8
]}

Li, M. ^{[1
,2
,3
]}

Winer, E. P. ^{[9
]}

Hudis, C. A. ^{[10
]}

Zembutsu, H. ^{[11
]}

Kubo, M. ^{[12
]}

Nakamura, Y. ^{[11
,12
,13
]}

McLeod, H. L. ^{[14
]}

Ratain, M. J. ^{[13
]}

Shulman, L. N. ^{[9
]}

Ritchie, M. D. ^{[7
]}

Plenge, R. M. ^{[5
,6
]}

Witte, J. S. ^{[3
,4
]}

Kroetz, D. L. ^{[1
,2
,3
]}

机构：

[1] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Therapeut Sci, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA

[4] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA

[5] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Div Genet, Boston, MA 02115 USA

[6] Broad Inst, Chem Biol Program, Med & Populat Genet Program, Cambridge, MA USA

[7] Penn State Univ, Eberly Coll Sci, Huck Inst Life Sci, Ctr Syst Genom,Dept Biochem & Mol Biol, University Pk, PA 16802 USA

[8] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA

[9] Dana Farber Canc Inst, Boston, MA 02115 USA

[10] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[11] Univ Tokyo, Mol Med Lab, Tokyo, Japan

[12] Riken Ctr, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[13] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[14] Univ N Carolina, Dept Pharmacol & Expt Therapeut, Chapel Hill, NC USA

来源：

PHARMACOGENOMICS JOURNAL | 2014年 / 14卷 / 04期

关键词：

heritability; neuropathy; paclitaxel; pathway; polygenic; TAXOL; NERVE; CISPLATIN; GROWTH; ASSOCIATION; EXPRESSION; GENOTYPE; CHEMOTHERAPY; SEQUENCE; DATABASE;

D O I：

10.1038/tpj.2014.2

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：336 / 342

页数：7

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