A comprehensive population-based study comparing the phenotype and genotype in a pretherapeutic screen of dihydropyrimidine dehydrogenase deficiency.
Aged
Cohort Studies
Cross-Sectional Studies
Dihydropyrimidine Dehydrogenase Deficiency
/ diagnosis
Dihydrouracil Dehydrogenase (NADP)
/ genetics
Female
France
/ epidemiology
Genotype
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Phenotype
Prevalence
Retrospective Studies
Uracil
/ analogs & derivatives
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
17
02
2020
accepted:
11
06
2020
revised:
02
06
2020
pubmed:
1
7
2020
medline:
1
4
2021
entrez:
30
6
2020
Statut:
ppublish
Résumé
Pretherapeutic screening for dihydropyrimidine dehydrogenase (DPD) deficiency is recommended or required prior to the administration of fluoropyrimidine-based chemotherapy. However, the best strategy to identify DPD-deficient patients remains elusive. Among a nationwide cohort of 5886 phenotyped patients with cancer who were screened for DPD deficiency over a 3 years period, we assessed the characteristics of both DPD phenotypes and DPYD genotypes in a subgroup of 3680 patients who had completed the two tests. The extent to which defective allelic variants of DPYD predict DPD activity as estimated by the plasma concentrations of uracil [U] and its product dihydrouracil [UH When [U] was used to monitor DPD activity, 6.8% of the patients were classified as having DPD deficiency ([U] > 16 ng/ml), while the [UH Frequent genetic DPYD variants have low performances in predicting partial DPD deficiency when evaluated by [U] alone, and [UH
Sections du résumé
BACKGROUND
Pretherapeutic screening for dihydropyrimidine dehydrogenase (DPD) deficiency is recommended or required prior to the administration of fluoropyrimidine-based chemotherapy. However, the best strategy to identify DPD-deficient patients remains elusive.
METHODS
Among a nationwide cohort of 5886 phenotyped patients with cancer who were screened for DPD deficiency over a 3 years period, we assessed the characteristics of both DPD phenotypes and DPYD genotypes in a subgroup of 3680 patients who had completed the two tests. The extent to which defective allelic variants of DPYD predict DPD activity as estimated by the plasma concentrations of uracil [U] and its product dihydrouracil [UH
RESULTS
When [U] was used to monitor DPD activity, 6.8% of the patients were classified as having DPD deficiency ([U] > 16 ng/ml), while the [UH
CONCLUSIONS
Frequent genetic DPYD variants have low performances in predicting partial DPD deficiency when evaluated by [U] alone, and [UH
Identifiants
pubmed: 32595208
doi: 10.1038/s41416-020-0962-z
pii: 10.1038/s41416-020-0962-z
pmc: PMC7462856
doi:
Substances chimiques
dihydrouracil
016FR52RU5
Uracil
56HH86ZVCT
Dihydrouracil Dehydrogenase (NADP)
EC 1.3.1.2
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
811-818Références
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