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

Journal Article (Journal Article)

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

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 (Pmeta=1.1×10), 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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • February 2018

Published In

Volume / Issue

  • 28 / 2

Start / End Page

  • 49 - 55

PubMed ID

  • 29278617

Pubmed Central ID

  • PMC5824720

Electronic International Standard Serial Number (EISSN)

  • 1744-6880

International Standard Serial Number (ISSN)

  • 1744-6872

Digital Object Identifier (DOI)

  • 10.1097/fpc.0000000000000318

Language

  • eng