Abstract
Aim: To evaluate toxicity risk in carriers of four DPYD variants using an institutional genetic repository. Materials & methods: Of over 65,000 patients in the repository, 582 were evaluated for the primary composite end point of grade 3 or higher toxicity or treatment modification due to toxicity. Results: The primary end point was more common in DPYD variant carriers (36.5vs18.1%, adjusted odds ratio 2.42, 95% CI: 1.05-5.55, p=0.04), and in patients with decreased DPD activity (≤1 vs 2) (75.6vs 17.0%, adjusted odds ratio 16.31, 95% CI: 2.64-100.68, p=0.003). Conclusion: Patients carrying any of the four DPYD variants are at increased risk of severe toxicity or subsequent treatment modifications, suggesting such patients may benefit from genotype-informed treatment.
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