DPYD Exome, mRNA Expression and Uracil Levels in Early Severe Toxicity to Fluoropyrimidines: An Extreme Phenotype Approach

Dihydropyrimidine dehydrogenase deficiency is a major cause of severe fluoropyrimidine-induced toxicity and could lead to interruption chemotherapy or life-threatening adverse reactions. This study aimed characterize the DPYD exon sequence, mRNA expression in vivo DPD activity by plasma uracil concentration. It was carried out two groups patients with extreme phenotypes (toxicity versus control) newly treated fluoropyrimidine, during first three cycles treatment. A novel nonsense gene variant (c.2197insA) most likely responsible for one patient, while neither nor concentration globally associated early toxicity. Our present work may help improve pharmacogenetic testing avoid undesirable reactions fluoropyrimidine treatment it also supports idea looking beyond DPYD.