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Updated: Apr 5, 2026

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
Dihydropyrimidinase and β-ureidopropionase gene variation and severe fluoropyrimidine-related toxicity
Dominic Kummer1,2, Tanja K Froehlich1, Markus Joerger3
1Institute of Clinical Chemistry, Inselspital, Bern University Hospital, & University of Bern, INO-F, CH-3010 Bern, Switzerland.
Aims:
To assess the association of DPYS and UPB1 genetic variation, encoding the catabolic enzymes downstream of dihydropyrimidine dehydrogenase, with early-onset toxicity from fluoropyrimidine-based chemotherapy.
Patients & Methods:
The coding and exon-flanking regions of both genes were sequenced in a discovery subset (164 patients). Candidate variants were genotyped in the full cohort of 514 patients.
Results & Conclusions:
Novel rare deleterious variants in DPYS (c.253C > T and c.1217G > A) were detected once each in toxicity cases and may explain the occurrence of severe toxicity in individual patients, and associations of common variants in DPYS (c.1-1T > C: p(adjusted) = 0.003; OR = 2.53; 95% CI: 1.39-4.62, and c.265-58T > C: p(adjusted) = 0.039; OR = 0.61; 95% CI: 0.38-0.97) with 5-fluorouracil toxicity were replicated.
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