Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing

Kristina Engvall; Hanna Uvdal; Niclas Björn; Elisabeth Åvall-Lundqvist; Henrik Gréen

doi:10.1038/s41698-024-00594-x

Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing

NPJ Precis Oncol. 2024 May 16;8(1):102. doi: 10.1038/s41698-024-00594-x.

Authors

Kristina Engvall^#¹, Hanna Uvdal^#², Niclas Björn², Elisabeth Åvall-Lundqvist³, Henrik Gréen^{2

4}

Affiliations

¹ Department of Oncology, Jönköping, Region Jönköping County, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. kristina.engvall@liu.se.
² Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
³ Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
⁴ Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.

^# Contributed equally.

Abstract

Persistent taxane-induced peripheral neuropathy (TIPN) is highly prevalent among early-stage breast cancer survivors (ESBCS) and has detrimental effect on quality of life. We leveraged logistic regression models to develop and validate polygenic prediction models to estimate the risk of persistent PN symptoms in a training cohort and validation cohort taking clinical risk factors into account. Based on 337 whole-exome sequenced ESBCS two of five prediction models for individual PN symptoms obtained AUC results above 60% when validated. Using the model for numbness in feet (35 SNVs) in the test cohort, 73% survivors were correctly predicted. For tingling in feet (55 SNVs) 70% were correctly predicted. Both models included SNVs from the ADAMTS20, APT6V0A2, CCDC88C, CYP2C8, EPHA5, NR1H3, PSKH2/APTV0D2, and SCN10A genes. For cramps in feet, difficulty climbing stairs and difficulty opening a jar the validation was unsuccessful. Polygenic prediction models including clinical risk factors can estimate the risk of persistent taxane-induced numbness in feet and tingling in feet in ESBCS.

Abstract

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