{"entity":{"id":"dpyd-genotyping","kind":"technology","name":"DPYD genotyping and DPD phenotyping before fluoropyrimidines","aka":["DPYD testing","DPD deficiency testing","dihydropyrimidine dehydrogenase test","uracil phenotyping","DPYD*2A"],"tldr":"A one-off blood test done before fluorouracil or capecitabine that finds the roughly one in twenty-five people who cannot break the drug down; halving their dose prevents severe and occasionally fatal toxicity without losing effect.","summary":"What it measures. Fluorouracil and its oral prodrug capecitabine are cleared by dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. About three to eight per cent of Europeans carry one of four well-characterised variants (DPYD*2A, *13, c.2846A>T, HapB3) that halve enzyme activity; very rare people carry two and have no enzyme at all. Genotyping reads these variants from blood or saliva. France and some other countries instead or additionally measure plasma uracil, the enzyme's natural substrate, which rises when DPD is deficient whatever the genetic cause (phenotyping).\n\nEvidence and guidelines. A prospective Dutch study of 1,103 patients (Lancet Oncology 2018) showed that reducing the starting dose in carriers cut severe toxicity to the level seen in non-carriers, and pharmacokinetic work showed exposure matched a normal dose. The Clinical Pharmacogenetics Implementation Consortium publishes the dose table: a 50 per cent starting dose reduction for heterozygous carriers and avoidance for homozygous or compound heterozygous patients, with the option to escalate on tolerance. In 2020 the European Medicines Agency recommended DPD testing before all fluoropyrimidine treatment; NHS England commissioned genotyping the same year, and most European countries followed. In the United States testing is recommended by several bodies and the drug labels warn of the risk, but it is not yet universal.\n\nWho should have it and what changes. Everyone about to start fluorouracil, capecitabine or tegafur, whatever the cancer. A normal result changes nothing. A carrier result lowers the starting dose, with careful escalation if tolerated; a complete deficiency means choosing a different drug. The test costs tens of pounds, comes back in a few days to a week, and needs doing once in a lifetime. The main gaps are variants common in non-European populations that the standard four-variant panel misses, and delays when the result is not back before cycle one.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Lancet Oncology 2018: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer, a prospective safety analysis","url":"https://doi.org/10.1016/S1470-2045(18)30686-7"},{"label":"CPIC guideline for fluoropyrimidines and DPYD","url":"https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/"},{"label":"EMA recommendations on DPD testing prior to treatment with fluorouracil, capecitabine, tegafur and flucytosine (2020)","url":"https://www.ema.europa.eu/en/news/ema-recommendations-dpd-testing-prior-treatment-fluorouracil-capecitabine-tegafur-and-flucytosine"}],"tags":[],"related":[],"cancers":["colorectal","gastric","pancreatic","breast-cancer","head-and-neck","anal","oesophageal-adenocarcinoma"],"sections":["diagnostics","chemotherapy","supportive-care"],"technologies":["oncology-pharmacogenomics","germline-testing","ugt1a1-genotyping","tpmt-nudt15-genotyping"],"targets":[],"drugs":["fluorouracil","capecitabine"],"companies":[],"institutions":["ema"],"pathways":[],"terms":["dose-modification","hand-foot-syndrome","mucositis","neutropenia","pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Targeted genotyping of DPYD variants that reduce dihydropyrimidine dehydrogenase activity, translated by consortium tables into an activity score and starting dose, optionally supplemented by plasma uracil measurement.","strengths":["Prevents severe and fatal toxicity in carriers","Cheap, once in a lifetime, guideline-mandated in Europe","Dose reduction does not reduce efficacy in prospective data"],"limitations":["Four-variant panels miss variants common outside European ancestry","Turnaround can delay the first cycle","Uptake in the United States and lower-income countries is patchy"],"since":2013},"route":"/technologies/dpyd-genotyping/","neighbours":{"cancer":[{"id":"anal","kind":"cancer","name":"Anal cancer (squamous cell carcinoma)","route":"/cancers/anal/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"oesophageal-adenocarcinoma","kind":"cancer","name":"Oesophageal and junctional adenocarcinoma","route":"/cancers/oesophageal-adenocarcinoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"oncology-pharmacogenomics","kind":"technology","name":"Pharmacogenomic testing before chemotherapy","route":"/technologies/oncology-pharmacogenomics/"},{"id":"tpmt-nudt15-genotyping","kind":"technology","name":"TPMT and NUDT15 genotyping before thiopurines","route":"/technologies/tpmt-nudt15-genotyping/"},{"id":"ugt1a1-genotyping","kind":"technology","name":"UGT1A1 genotyping before irinotecan","route":"/technologies/ugt1a1-genotyping/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"}],"institution":[{"id":"ema","kind":"institution","name":"European Medicines Agency","route":"/institutions/ema/"}],"term":[{"id":"dose-modification","kind":"term","name":"Dose reduction, interruption and discontinuation","route":"/terms/dose-modification/"},{"id":"hand-foot-syndrome","kind":"term","name":"Hand-foot syndrome and hand-foot skin reaction","route":"/terms/hand-foot-syndrome/"},{"id":"mucositis","kind":"term","name":"Mucositis and stomatitis","route":"/terms/mucositis/"},{"id":"neutropenia","kind":"term","name":"Neutropenia","route":"/terms/neutropenia/"},{"id":"pharmacokinetics","kind":"term","name":"Pharmacokinetics (PK), half-life and exposure","route":"/terms/pharmacokinetics/"}]}}