title: [Review of methods for determination of dihydropyrimidine dehydrogenase and possible application in screening previous chemotheraphy with 5-fluorouracil].
abstract: 5-fluorouracil (5-FU) and its prodrug capecitabine are one of the most commonly used chemotherapeutic drugs. DPD-deficient cancer patients may be at risk of severe and sometimes lethal toxicity after the administration of 5-FU. In 39-61% of the cases severe toxicity of 5-FU is caused by decreased DPD acivity. DPD is the initial and rate-limiting enzyme of the metabolism of pyrimidines. 80-90% of the administered 5-FU is catabolised by DPD. Mutation of the DPYD gene encoding DPD result in decreased enzyme activity--total (0.2% of population) or partial (3-5% of population). Determination of DPD activity can be used as a screening procedure to identify patients with a DPD deficiency, before the start of treatment with 5-FU. There are several methods for DPD activity determination: the detection of relevant DPYD gene single-nucleotide polymorphism (SNPs), measurement of the level of DPYDmRNA expression, the evaluation of DPD activity in PBMC, the measurement of uracil in plasma and urea, evaluation of the UH2/U (dihydrouracil/uracil) and THYH2/THY (dihydrothymine/tymine) ratio in plasma and urea, [2-C13]uracil breath test, the analysis of fluorouracil and dihydrofluorouracil in plasma after administered a test dose of fluorouracil and measurement of 2-fluoro-beta-alanine. So far more than 30 mutations of DPYD gene have been identified in patients with cancer. A large number of them limits introduction of simple genetic test, which could be used for detection of DPD deficiency. Therefore scientists in searching of the simplest, the cheapest and the most available technique for detection DPD deficiency, generally use methods associated with measurement of DPD activity.
authors: Katedra Diagnostyki Laboratoryjnej i Medycyny Molekulamej, Pomorski Uniwersytet Medyczny, Szczecin. aostapowicz@op.pl
authors: Anna
authors: A
authors: Ostapowicz
authors: Barbara
authors: B
authors: Dołegowska
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D000069287:Capecitabine; D015897:Comorbidity; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D054067:Dihydropyrimidine Dehydrogenase Deficiency / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D005472:Fluorouracil / Q000009:adverse effects* / Q000031:analogs & derivatives*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis; D014498:Uracil / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D012333:RNA, Messenger; D003841:Deoxycytidine; D014498:Uracil; D000069287:Capecitabine; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil