Advanced statistics identifcation of participant and treatment predictors associated with severe adverse efects induced by fuoropyrimidine‑based chemotherapy

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dc.contributor.authorKorver, S.K.
dc.contributor.authorBowen, J.M.
dc.contributor.authorGibson, R.J.
dc.contributor.authorBall, I.A.
dc.contributor.authorSecombe, K.R.
dc.contributor.authorWain, T.J.
dc.contributor.authorLogan, R.M.
dc.contributor.authorTuke, J.
dc.contributor.authorMead, K.R.
dc.contributor.authorRichards, A.M.
dc.contributor.authorKarapetis, C.S.
dc.contributor.authorKeefe, D.M.
dc.contributor.authorColler, J.K.
dc.date.issued2023
dc.description.abstractPURPOSE: Adverse effects following fluoropyrimidine-based chemotherapy regimens are common. However, there are no current accepted diagnostic markers for prediction prior to treatment, and the underlying mechanisms remain unclear. This study aimed to determine genetic and non-genetic predictors of adverse effects. METHODS: Genomic DNA was analyzed for 25 single nucleotide polymorphisms (SNPs). Demographics, comorbidities, cancer and fluoropyrimidine-based chemotherapy regimen types, and adverse effect data were obtained from clinical records for 155 Australian White participants. Associations were determined by bivariate analysis, logistic regression modeling and Bayesian network analysis. RESULTS: Twelve different adverse effects were observed in the participants, the most common severe adverse effect was diarrhea (12.9%). Bivariate analysis revealed associations between all adverse effects except neutropenia, between genetic and non-genetic predictors, and between 8 genetic and 12 non-genetic predictors with more than 1 adverse effect. Logistic regression modeling of adverse effects revealed a greater/sole role for six genetic predictors in overall gastrointestinal toxicity, nausea and/or vomiting, constipation, and neutropenia, and for nine non-genetic predictors in diarrhea, mucositis, neuropathy, generalized pain, hand-foot syndrome, skin toxicity, cardiotoxicity and fatigue. The Bayesian network analysis revealed less directly associated predictors (one genetic and six non-genetic) with adverse effects and confirmed associations between six adverse effects, eight genetic predictors and nine non-genetic predictors. CONCLUSION: This study is the first to link both genetic and non-genetic predictors with adverse effects following fluoropyrimidine-based chemotherapy. Collectively, we report a wealth of information that warrants further investigation to elucidate the clinical significance, especially associations with genetic predictors and adverse effects.
dc.description.statementofresponsibilitySamantha K. Korver, Joanne M. Bowen, Rachel J. Gibson, Imogen A. Ball, Kate R. Secombe, Taylor J. Wain, Richard M. Logan, Jonathan Tuke, Kelly R. Mead, Alison M. Richards, Christos S. Karapetis, Dorothy M. Keefe, Janet K. Coller
dc.identifier.citationCancer Chemotherapy and Pharmacology, 2023; 91(6):507-521
dc.identifier.doi10.1007/s00280-023-04538-3
dc.identifier.issn0344-5704
dc.identifier.issn1432-0843
dc.identifier.orcidKorver, S.K. [0000-0001-7670-3093]
dc.identifier.orcidBowen, J.M. [0000-0003-0876-0031]
dc.identifier.orcidGibson, R.J. [0000-0002-4796-1621]
dc.identifier.orcidBall, I.A. [0000-0002-9629-9064]
dc.identifier.orcidSecombe, K.R. [0000-0003-0716-238X]
dc.identifier.orcidLogan, R.M. [0000-0002-9331-1814]
dc.identifier.orcidTuke, J. [0000-0002-1688-8951]
dc.identifier.orcidKeefe, D.M. [0000-0001-9377-431X]
dc.identifier.orcidColler, J.K. [0000-0002-8273-5048]
dc.identifier.urihttps://hdl.handle.net/2440/141857
dc.language.isoen
dc.publisherSpringer Science and Business Media LLC
dc.rights© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1007/s00280-023-04538-3
dc.subjectFluoropyrimidine-based chemotherapy; Adverse efects; Risk; Logistic modeling; Bayesian network analysis
dc.subject.meshHumans
dc.subject.meshNeutropenia
dc.subject.meshDiarrhea
dc.subject.meshFluorouracil
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshAntimetabolites
dc.subject.meshBayes Theorem
dc.subject.meshAustralia
dc.subject.meshDrug-Related Side Effects and Adverse Reactions
dc.titleAdvanced statistics identifcation of participant and treatment predictors associated with severe adverse efects induced by fuoropyrimidine‑based chemotherapy
dc.typeJournal article
pubs.publication-statusPublished

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