Genotype-Phenotype Predictive Gap in Pre-Emptive Screening of DPD Deficiency: Improving Sensitivity

Background/Objectives: toxicity related to treatment with the anti-cancer drugs fluoropyrimidines (FP) is mainly driven by a deficiency in the dihydropyrimidine-dehydrogenase (DPD) enzyme activity. Standardized pharmacogenomic markers in the DPYD gene allow pre-emptive prediction and therapy adjustment in patients testing positive, but the rarity of these markers lowers screening sensitivity, leaving a significant part of at-risk individuals undetected. This study aimed to explore the diagnostic performance of genetic screening tests modelled to include unclassified rare DPYD variants and the common SNPs rs1801160 and rs2297595.