Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis.

The syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency is an uncommon but well-described cause of severe toxicity related to fluoropyrimidine chemotherapy agents (5-fluorouracil and capecitabine). Patients with latent DPD deficiency can be identified preemptively with genotyping of the DPYD gene, or with measurement of the plasma uracil concentration. In this systematic review and meta-analysis, the authors study the rare outcome of treatment-related death after fluoropyrimidine chemotherapy. DPYD gene variants associated with DPD deficiency were linked to a 25.6 times increased risk of fluoropyrimidine-related mortality. These findings support the clinical utility of DPYD genotyping as a screening test for DPD deficiency.