Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/222221
Title: DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
Author: Otero Torres, Sara
Rodríguez Mauriz, Rosa
Fort Casamartina, Eduard
Clopés Estela, Ana
Soler Rotllant, Francesc
Fontanals Martínez, Sandra
Montero Pérez, Olalla
Keywords: Medicaments antineoplàstics
Toxicologia genètica
Antineoplastic agents
Genetic toxicology
Issue Date: 15-May-2025
Publisher: MDPI
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.3390/ph18050727
It is part of: Pharmaceuticals, 2025, vol. 18, num. 5, 727
URI: https://hdl.handle.net/2445/222221
Related resource: https://doi.org/10.3390/ph18050727
ISSN: 1424-8247
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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