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Dihydropyrimidine dehydrogenase (DPYD) genetic testing and treatment with 5-fluoropyrimidines in cancer patients: prevalence of variants with decreased activity and chemotherapy outcomes
Journal article   Peer reviewed

Dihydropyrimidine dehydrogenase (DPYD) genetic testing and treatment with 5-fluoropyrimidines in cancer patients: prevalence of variants with decreased activity and chemotherapy outcomes

Christopher Rosso, Michela Febbraro and Ioannis A Voutsadakis
Pharmacogenomics
03/09/2026
DOI: 10.1080/14622416.2026.2641748
PMCID: PMC13078210
PMID: 41797628

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Abstract

Fluoropyrimidines are among the most useful drugs in oncology with an established record of efficacy and safety. A minority of oncology patients bear genetic variants with reduced activity of the main enzyme catabolizing these drugs, dihydropyrimidine dehydrogenase (DPYD) and may be prone to severe or even lethal adverse effects. We reviewed the records of gastrointestinal and breast cancer patients treated in our cancer center for the identification of cases that had DPYD genetic testing for variants and received treatment with fluoropyrimidines. The records of patients fulfilling these criteria were retrieved, and the prevalence of the different variants and their clinical implications and outcomes were recorded. The overall prevalence of four common DPYD variants was 7.3% (10 of 137 patients). Most prevalent variant was the haplotype HapB3 (five patients, 3.6%), followed by the DPYD p.D949V variant (3 patients, 2.2%), while one patient each (0.7%) had the two null variants DPYD*2A and DPYD*13. A sizable minority of oncology patients bear variants of DPYD with reduced activity and may be at increased risk of fluoropyrimidine toxicities if treated at full doses. However, variability within the same genotype exists.
 Chemotherapy Drug Metabolism Fluoropyrimidines genomic variants DPYD

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