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DPYD False Negative — SCE Medical Oncology MCQ

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HardGI CancersDPYD False NegativeSCE Medical Oncology

A 60-year-old man with rectal cancer on neoadjuvant capecitabine-CRT develops DPD deficiency symptoms (severe mucositis, myelosuppression) despite having had pre-treatment DPYD testing showing no identified variant. What explains this?

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Correct answer: E — Standard DPYD genotyping tests only the 4 most common European variants and has approximately 30-50% sensitivity for detecting all DPD-deficient patients — phenotypic DPD deficiency from rare/uncharacterised variants or epigenetic silencing can still occur

Standard DPYD pharmacogenomic testing (4 variants: *2A, c.2846A>T, c.1679T>G, c.1236G>A/HapB3) detects only approximately 30-50% of all DPD-deficient patients. The remaining deficiency comes from rare variants not on standard panels, epigenetic DPYD promoter methylation, and phenotypic DPD deficiency without identifiable genotypic cause. Phenotypic testing (DPD enzyme activity assay or uracil/dihydrouracil ratio) may identify additional at-risk patients. Severe toxicity despite normal genotyping should prompt emergency uridine triacetate (Vistogard) if available.

Reference: NICE DG58; ESMO Pharmacogenomics; Henricks et al Clin Pharmacol Ther 2018