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. 2025 Apr 8;33(5):362.
doi: 10.1007/s00520-025-09392-y.

Pharmacogenomics of chemotherapy induced peripheral neuropathy using an electronic health record-derived definition: a genome-wide association study

Michael K Jones  1 , Andrew Nicklawsky  2 , Jonathan Shortt  3   4 , Jack Pattee  5   4 , Victoria Kennerley  3   4 , Corbin J Eule  6 , Nellowe Candelario  7 ; Biobank at the Colorado Center for Personalized Medicine (Banner Authorship); Peter H O'Donnell  8 , Thomas W Flaig  6
Affiliations

Pharmacogenomics of chemotherapy induced peripheral neuropathy using an electronic health record-derived definition: a genome-wide association study

Michael K Jones et al. Support Care Cancer. .

Abstract

Purpose: Prior studies evaluating the genetic predisposition to chemotherapy induced peripheral neuropathy (CIPN) have been limited by small populations due to difficulty with real-world data extraction. This genome-wide association study (GWAS) evaluates the genetic differences between patients who developed CIPN against those unaffected, using an electronic health record (EHR) definition of CIPN.

Methods: This study included all patients who received chemotherapy associated with CIPN and had germline genetic data within the biobank at the Colorado Center for Personalized Medicine. CIPN was defined by a new neuropathic pain medication or an ICD-diagnosis of neuropathy after specified chemotherapy initiation. GWAS were stratified by (1) total population, (2) platinum chemotherapy, (3) taxane chemotherapy, and (4) vinca alkaloid chemotherapy. Genes previously associated with CIPN were analyzed within each GWAS.

Results: Nine hundred fifteen patients received chemotherapy associated with CIPN, with 528 patients (57%) developing CIPN. Median age at chemotherapy initiation was 60.5 years; female sex (n = 517, 56.5%) and White or Caucasian race (n = 822, 89.8%) were most common. Among single nucleotide polymorphisms (SNPs) that reached suggestive levels of genome-wide significance (p < 1 × 10-5), 60 SNPs occurred within 11 genes that may play a role in the development of or protection against CIPN, including RCOR1, CLDN14, TRIM5, and TMC2. No SNPs previously associated with CIPN achieved genome-wide significance in this population.

Conclusion: This pharmacogenomic study suggests several genomic loci that may modulate the development of CIPN. This EHR-definition may allow for increased sample sizes and improved statistical power in future genetic studies of CIPN.

Keywords: Chemotherapy-induced peripheral neuropathy; Electronic health record; Genome-wide association study; Personalized medicine; Pharmacogenomics.

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Conflict of interest statement

Declarations. Ethics approval: This project was approved by the Colorado Multiple Institutional Review Board, PAM001-1. Actions by COMIRB [are] guided by the principles of respect for persons, beneficence, and justice set forth in the Ethical Principles and Guidelines for the Protection of Human Subjects of Research (often referred to as the Belmont Report). Competing interests: The authors have no relevant financial or non-financial interests to disclose.

References

    1. Argyriou AA, et al Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. (1879–0461 (Electronic)).
    1. Hershman DL, et al., (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. (1527–7755 (Electronic)).
    1. Chan A et al (2019) Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview. Support Care Cancer 27(10):3729–3737 - DOI - PubMed - PMC
    1. Shriver SP et al (2024) Overcoming barriers to discovery and implementation of equitable pharmacogenomic testing in oncology. J Clin Oncol 42(10):1181–1192 - DOI - PubMed - PMC
    1. de With M et al (2023) Implementation of dihydropyrimidine dehydrogenase deficiency testing in Europe. ESMO Open 8(2) - DOI - PubMed - PMC

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