New Fluoropyrimidine Toxicity Variants Reported in DPYS and PPARD

A recent paper highlights new variants and genes associated with severe fluoropyrimidine-related toxicity in patients who were genotyped as negative for the four DPYD variants the European Medicines Agency recommends testing for.

Online ahead of print in the Human Genomics journal is De Mattia et al "The burden of rare variants in DPYS gene is a novel predictor of the risk of developing severe fluoropyrimidine-related toxicity" [PMID: 37946254].

The study sequenced 120 patients with fluoropyrimidine induced grade 3-5 toxicity confirming they lacked DPYD*2A, DPYD*13, c.2846A > T, c.1236G > A-HapB3. The paper reports rare and common variants including DPYS rs143004875-T and PPARD rs2016520-T which were associated with increased risk of severe toxicity.