Common dihydropyrimidinase ( DPYS ) genetic variations do not predict fluoropyrimidine-related chemotherapy toxicity in a Canadian cohort.
Pharmacogenet Genomics
; 34(3): 83-87, 2024 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-38215018
ABSTRACT
Known genetic variations in dihydropyrimidine dehydrogenase (gene name DPYD ) do not fully predict patients at risk for severe fluoropyrimidine-associated chemotherapy toxicity. Dihydropyrimidinase (gene name DPYS ), the second catabolic enzyme in fluoropyrimidine metabolism, has been noted as a potential determinant of variation in fluoropyrimidine metabolism and response. In this study, we genotyped for DPYS c.-1T>C (rs2959023), c.265-58T>C (rs2669429) and c.541C>T (rs36027551) in a Canadian cohort of 248 patients who were wild type for Clinical Pharmacogenetics Implementation Consortium recommended DPYD variants and had received a standard dose of fluoropyrimidine chemotherapy. None of our patients were found to carry the DPYS c.541C>T variant, while the minor allele frequencies were 63% and 54% for c.-1T>C and c.265-58T>C, respectively. There was no association between DPYS c.-1T>C wild type and heterozygote [odds ratio (OR) (95% confidence interval, CI) = 1.10 (0.51-2.40)] or homozygote variant carriers [OR (95% CI)â
=â
1.22 (0.55-2.70)], or between DPYS c.265-58T>C wild-type patients and heterozygote [OR (95% CI)â
=â
0.93 (0.48-1.80)] or homozygote variant carriers [OR (95% CI)â
=â
0.76 (0.37-1.55)] in terms of fluoropyrimidine-associated toxicity. Therefore, in our cohort of mostly Caucasian Canadians, genetic variations in DPYS do not appear to be a significant contributor to severe fluoropyrimidine-associated toxicity.
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Base de dados:
MEDLINE
Assunto principal:
Di-Hidrouracila Desidrogenase (NADP)
/
Fluoruracila
/
Antimetabólitos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article