Identification of additional DPYD polymorphisms that increase the risk of severe fluoropyrimidine toxicity and improved predictive accuracy when combined with previously validated variants - PubMed
4 hours ago
- #chemotherapy safety
- #fluoropyrimidine toxicity
- #DPYD polymorphisms
- Study identifies additional DPYD polymorphisms increasing fluoropyrimidine (FP) toxicity risk.
- Four DPYD polymorphisms (*2A, *13, p.Asp949Val, HapB3) are already known to increase FP toxicity risk.
- The study included 849 adult patients treated with FP chemotherapy for any cancer.
- Primary endpoint was grade ≥3 toxicity or treatment modification in the first two FP cycles.
- Five uncommon DPYD variants (1.1% of patients) significantly increased toxicity risk (67% vs. 24%).
- Common DPYD variants were not associated with increased toxicity risk.
- Combining uncommon and validated variants slightly improved toxicity prediction (PPV: 44.1% vs. 40.0%).
- Testing these uncommon variants could help identify more high-risk patients for adjusted FP doses.