DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews

Background/Objectives: Fluoropyrimidines are widely used chemotherapeutic agents in various solid tumors. Germline variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), are known to impair drug metabolism and increase the risk of severe toxicity. This umbrella re...

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Autores: Otero Torres, Sara, Rodríguez Mauriz, Rosa, Fort Casamartina, Eduard, Clopés Estela, Ana, Soler Rotllant, Francesc, Fontanals Martínez, Sandra, Montero Pérez, Olalla
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/222221
Acceso en línea:https://hdl.handle.net/2445/222221
Access Level:acceso abierto
Palabra clave:Medicaments antineoplàstics
Toxicologia genètica
Antineoplastic agents
Genetic toxicology
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spelling DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic ReviewsOtero Torres, SaraRodríguez Mauriz, RosaFort Casamartina, EduardClopés Estela, AnaSoler Rotllant, FrancescFontanals Martínez, SandraMontero Pérez, OlallaMedicaments antineoplàsticsToxicologia genèticaAntineoplastic agentsGenetic toxicologyBackground/Objectives: Fluoropyrimidines are widely used chemotherapeutic agents in various solid tumors. Germline variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), are known to impair drug metabolism and increase the risk of severe toxicity. This umbrella review aims to synthesize the current evidence from systematic reviews on the association between DPYD variants and fluoropyrimidine-induced toxicity. Methods: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library from inception to 2023, including gray literature. Systematic reviews assessing fluoropyrimidine toxicity in oncologic patients with DPYD variants were included. Study quality was assessed using the AMSTAR-2 tool. Registration number in PROSPERO: CRD42023401226. Results: Two independent investigators performed the study selection, quality assessment, and data collection. Eight systematic reviews met the inclusion criteria. Methodological confidence was rated as critically low in six, low in one, and medium in another one. The reviews included 125 primary studies, most of them focused on four key DPYD variants (DPYD2*A, DPYD*13, c.2846A>T, and HapB3), all of which showed consistent associations with an increased risk of severe toxicity. Rare variants such as DPYD*4, *5, and *6 were also examined, though evidence remains limited. Pharmacogenetics-guided dosing of fluoropyrimidines significantly reduced toxicity rates in several studies. The integration of DPYD genotyping with phenotyping approaches faces limitations; these tests should complement rather than replace genotyping information. Conclusions: This umbrella review confirms the clinical relevance of DPYD genotyping to predict and mitigate fluoropyrimidine toxicity. Incorporating genotyping into clinical practice, potentially alongside phenotyping and therapeutic drug monitoring, may enhance patient safety and treatment efficacy.MDPI2025202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfhttps://hdl.handle.net/2445/222221Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/ph18050727Pharmaceuticals, 2025, vol. 18, num. 5, 727https://doi.org/10.3390/ph18050727cc-by (c) Otero Torres, Sara et al., 2025http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2222212026-05-29T05:05:01Z
dc.title.none.fl_str_mv DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
title DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
spellingShingle DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
Otero Torres, Sara
Medicaments antineoplàstics
Toxicologia genètica
Antineoplastic agents
Genetic toxicology
title_short DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
title_full DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
title_fullStr DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
title_full_unstemmed DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
title_sort DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
dc.creator.none.fl_str_mv Otero Torres, Sara
Rodríguez Mauriz, Rosa
Fort Casamartina, Eduard
Clopés Estela, Ana
Soler Rotllant, Francesc
Fontanals Martínez, Sandra
Montero Pérez, Olalla
author Otero Torres, Sara
author_facet Otero Torres, Sara
Rodríguez Mauriz, Rosa
Fort Casamartina, Eduard
Clopés Estela, Ana
Soler Rotllant, Francesc
Fontanals Martínez, Sandra
Montero Pérez, Olalla
author_role author
author2 Rodríguez Mauriz, Rosa
Fort Casamartina, Eduard
Clopés Estela, Ana
Soler Rotllant, Francesc
Fontanals Martínez, Sandra
Montero Pérez, Olalla
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Medicaments antineoplàstics
Toxicologia genètica
Antineoplastic agents
Genetic toxicology
topic Medicaments antineoplàstics
Toxicologia genètica
Antineoplastic agents
Genetic toxicology
description Background/Objectives: Fluoropyrimidines are widely used chemotherapeutic agents in various solid tumors. Germline variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), are known to impair drug metabolism and increase the risk of severe toxicity. This umbrella review aims to synthesize the current evidence from systematic reviews on the association between DPYD variants and fluoropyrimidine-induced toxicity. Methods: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library from inception to 2023, including gray literature. Systematic reviews assessing fluoropyrimidine toxicity in oncologic patients with DPYD variants were included. Study quality was assessed using the AMSTAR-2 tool. Registration number in PROSPERO: CRD42023401226. Results: Two independent investigators performed the study selection, quality assessment, and data collection. Eight systematic reviews met the inclusion criteria. Methodological confidence was rated as critically low in six, low in one, and medium in another one. The reviews included 125 primary studies, most of them focused on four key DPYD variants (DPYD2*A, DPYD*13, c.2846A>T, and HapB3), all of which showed consistent associations with an increased risk of severe toxicity. Rare variants such as DPYD*4, *5, and *6 were also examined, though evidence remains limited. Pharmacogenetics-guided dosing of fluoropyrimidines significantly reduced toxicity rates in several studies. The integration of DPYD genotyping with phenotyping approaches faces limitations; these tests should complement rather than replace genotyping information. Conclusions: This umbrella review confirms the clinical relevance of DPYD genotyping to predict and mitigate fluoropyrimidine toxicity. Incorporating genotyping into clinical practice, potentially alongside phenotyping and therapeutic drug monitoring, may enhance patient safety and treatment efficacy.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/222221
url https://hdl.handle.net/2445/222221
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ph18050727
Pharmaceuticals, 2025, vol. 18, num. 5, 727
https://doi.org/10.3390/ph18050727
dc.rights.none.fl_str_mv cc-by (c) Otero Torres, Sara et al., 2025
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Otero Torres, Sara et al., 2025
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 18 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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