Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci

Lara E. Sucheston-Campbell, Alyssa I. Clay-Gilmour, William E. Barlow, G. Thomas Budd, Daniel O. Stram, Christopher A. Haiman, Xin Sheng, Li Yan, Gary Zirpoli, Song Yao, Chen Jiang, Kouros Owzar, Dawn Hershman, Kathy S. Albain, Daniel F. Hayes, Halle C. Moore, Timothy J. Hobday, James A. Stewart, Abbas Rizvi, Claudine IsaacsMuhammad Salim, Jule R. Gralow, Gabriel N. Hortobagyi, Robert B Livingston, Deanna L. Kroetz, Christine B. Ambrosone

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk variants for TIPN. Patients and methods Women with high-risk breast cancer enrolled in SWOG 0221 were genotyped using the Illumina 1M chip. Genome-wide analyses were performed in relation to ≥grade 3 Common Terminology Criteria for Adverse Events (CTCAE) neuropathy in European and African Americans. Data were meta-analyzed with GW associations of CTCAE ≥grade 3 versus <grade 3 in CALGB 40101 assuming a fixed effects model. Results The percentage of ≥grade 3 TIPN in 1269 European Americans and 139 African Americans in S0221, was 11.6 and 22.3%, respectively. CALGB 40101 ≥grade 3 TOPN was 7.2%. The most significant association with ≥grade 3 TIPN was the G allele of rs1858826 in GNGT1 (P meta =1.1×10 -7), which showed a decrease in risk of ≥grade 3 TIPN (odds ratio=0.29, 95% confidence interval: 0.18-0.46). Conclusion The genetic variants associated with ≥grade 3 TIPN are hypothesized to have biochemical functions and reside in and near genes involved in diabetes and diabetic neuropathy. This finding is consistent with results from CALGB 40101 pathway analyses. Larger homogeneous trials with similar dosing and criteria for defining neuropathy are needed to properly assess the relationship of genomics with the neuropathy spectrum.

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalPharmacogenetics and Genomics
Volume28
Issue number2
DOIs
StatePublished - Jan 1 2018

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Peripheral Nervous System Diseases
Meta-Analysis
Genome
Terminology
African Americans
Breast Neoplasms
Diabetic Neuropathies
Genomics
taxane
Alleles
Odds Ratio
Confidence Intervals
Drug Therapy
Survival
Genes

Keywords

  • breast cancer
  • genome-wide association study
  • neuropathy
  • taxane

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Sucheston-Campbell, L. E., Clay-Gilmour, A. I., Barlow, W. E., Budd, G. T., Stram, D. O., Haiman, C. A., ... Ambrosone, C. B. (2018). Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci. Pharmacogenetics and Genomics, 28(2), 49-55. https://doi.org/10.1097/FPC.0000000000000318

Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci. / Sucheston-Campbell, Lara E.; Clay-Gilmour, Alyssa I.; Barlow, William E.; Budd, G. Thomas; Stram, Daniel O.; Haiman, Christopher A.; Sheng, Xin; Yan, Li; Zirpoli, Gary; Yao, Song; Jiang, Chen; Owzar, Kouros; Hershman, Dawn; Albain, Kathy S.; Hayes, Daniel F.; Moore, Halle C.; Hobday, Timothy J.; Stewart, James A.; Rizvi, Abbas; Isaacs, Claudine; Salim, Muhammad; Gralow, Jule R.; Hortobagyi, Gabriel N.; Livingston, Robert B; Kroetz, Deanna L.; Ambrosone, Christine B.

In: Pharmacogenetics and Genomics, Vol. 28, No. 2, 01.01.2018, p. 49-55.

Research output: Contribution to journalArticle

Sucheston-Campbell, LE, Clay-Gilmour, AI, Barlow, WE, Budd, GT, Stram, DO, Haiman, CA, Sheng, X, Yan, L, Zirpoli, G, Yao, S, Jiang, C, Owzar, K, Hershman, D, Albain, KS, Hayes, DF, Moore, HC, Hobday, TJ, Stewart, JA, Rizvi, A, Isaacs, C, Salim, M, Gralow, JR, Hortobagyi, GN, Livingston, RB, Kroetz, DL & Ambrosone, CB 2018, 'Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci', Pharmacogenetics and Genomics, vol. 28, no. 2, pp. 49-55. https://doi.org/10.1097/FPC.0000000000000318
Sucheston-Campbell LE, Clay-Gilmour AI, Barlow WE, Budd GT, Stram DO, Haiman CA et al. Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci. Pharmacogenetics and Genomics. 2018 Jan 1;28(2):49-55. https://doi.org/10.1097/FPC.0000000000000318
Sucheston-Campbell, Lara E. ; Clay-Gilmour, Alyssa I. ; Barlow, William E. ; Budd, G. Thomas ; Stram, Daniel O. ; Haiman, Christopher A. ; Sheng, Xin ; Yan, Li ; Zirpoli, Gary ; Yao, Song ; Jiang, Chen ; Owzar, Kouros ; Hershman, Dawn ; Albain, Kathy S. ; Hayes, Daniel F. ; Moore, Halle C. ; Hobday, Timothy J. ; Stewart, James A. ; Rizvi, Abbas ; Isaacs, Claudine ; Salim, Muhammad ; Gralow, Jule R. ; Hortobagyi, Gabriel N. ; Livingston, Robert B ; Kroetz, Deanna L. ; Ambrosone, Christine B. / Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci. In: Pharmacogenetics and Genomics. 2018 ; Vol. 28, No. 2. pp. 49-55.
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