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Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-6806-4527
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
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2024 (English)In: npj Precision Oncology, E-ISSN 2397-768X, Vol. 8, no 1, article id 102Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PORTFOLIO , 2024. Vol. 8, no 1, article id 102
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Cancer and Oncology
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URN: urn:nbn:se:liu:diva-204339DOI: 10.1038/s41698-024-00594-xISI: 001227003700002PubMedID: 38755266OAI: oai:DiVA.org:liu-204339DiVA, id: diva2:1868635
Note

Funding Agencies|Swedish Research Council; Knut and Alice Wallenberg Foundation; Swedish Cancer Society [22 2202]; Swedish governmental funding of clinical research (ALF) [ROE-975072]; Medical Research Council of Southeast Sweden [FORSS 941224]; Futurum-the academy for health and care, Region Jonkoping County [FUTURUM-975687]

Available from: 2024-06-12 Created: 2024-06-12 Last updated: 2024-06-12

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Engvall, KristinaUvdal, HannaBjörn, NiclasÅvall Lundqvist, ElisabethGreen, Henrik
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDivision of Clinical Chemistry and PharmacologyDepartment of Oncology
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