DPYD Exome, mRNA Expression and Uracil Levels in Early Severe Toxicity to Fluoropyrimidines: An Extreme Phenotype Approach

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Villalvazo, Priscila and Marzal Alfaro, Belén and García Alfonso, Pilar and Revuelta Herrero, José Luis and Thomas, Fabienne and López Tarruella, Sara and García González, Xandra and Calvo, Aitana and Yakoubi, Malika and Salvador Martín, Sara and López López, Flora and Aguilar, Iker and Sanjurjo Sáez, María and Martín, Miguel and López Fernández, Luis Andrés (2021) DPYD Exome, mRNA Expression and Uracil Levels in Early Severe Toxicity to Fluoropyrimidines: An Extreme Phenotype Approach. Journal of Personalized Medicine, 11 (8). p. 792. ISSN 2075-4426

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Official URL: https://doi.org/10.3390/jpm11080792




Abstract

Dihydropyrimidine dehydrogenase deficiency is a major cause of severe fluoropyrimidine-induced toxicity and could lead to interruption of chemotherapy or life-threatening adverse reactions. This study aimed to characterize the DPYD exon sequence, mRNA expression and in vivo DPD activity by plasma uracil concentration. It was carried out in two groups of patients with extreme phenotypes (toxicity versus control) newly treated with a fluoropyrimidine, during the first three cycles of treatment. A novel nonsense gene variant (c.2197insA) was most likely responsible for fluoropyrimidine-induced toxicity in one patient, while neither DPYD mRNA expression nor plasma uracil concentration was globally associated with early toxicity. Our present work may help improve pharmacogenetic testing to avoid severe and undesirable adverse reactions to fluoropyrimidine treatment and it also supports the idea of looking beyond DPYD.


Item Type:Article
Uncontrolled Keywords:pharmacogenetics; cancer; adverse drug events; capecitabine; 5-fluorouracil
Subjects:Medical sciences > Medicine > Pharmacology
Medical sciences > Medicine > Oncology
ID Code:71663
Deposited On:20 Apr 2022 14:36
Last Modified:20 Apr 2022 14:51

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