DPYD c.85 T > C, DPYD c.496 A>G, and DPYD c.2194 G>A and severe toxicity to fluoropyrimidines in PREPARE and Alpe-DPD trials. An original study and meta-analysis.
Pharmacol ResSep 11, 2026 (epub)
Elena De Mattia, Jerry Polesel, Maaike van der Lee et al.
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In 30 seconds
This meta-analysis evaluated the impact of DPYD variants on severe toxicity from fluoropyrimidines in 17,485 patients across multiple studies, including the PREPARE and Alpe-DPD trials. It found that DPYD c.2194 G>A and c.496 A>G were associated with increased toxicity risk (OR=1.70 and OR=1.55, respectively), while c.85 T > C improved risk prediction in haplotype analysis.
Key findings
- DPYD c.2194 G>A was associated with severe FL toxicity (OR=1.70; 95%CI: 1.48-1.95).
- DPYD c.496 A>G increased toxicity risk (OR=1.55; 95%CI: 1.19-2.02).
- Haplotype #3 was linked to severe overall toxicity (OR=2.62 in PREPARE).
- Haplotype #3 showed significant gastrointestinal toxicity (OR=5.65 in PREPARE).
Why it matters
Understanding the genetic factors influencing fluoropyrimidine toxicity can enhance patient safety and treatment efficacy. This study highlights the importance of refining pharmacogenetic testing to better predict adverse reactions, potentially guiding personalized treatment strategies.