{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:14:14Z","timestamp":1791389654395,"version":"4.3.3"},"reference-count":46,"publisher":"Walter de Gruyter GmbH","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2024-0317_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of severe fluoropyrimidine-related toxicities. The best strategy for identifying DPD-deficient patients is still not defined. The EMA recommends targeted <jats:italic>DPYD<\/jats:italic> genotyping or uracilemia (U)\u00a0testing. We analyzed the concordance between both approaches.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2024-0317_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study included 19,376 consecutive French patients with pre-treatment plasma U, UH2 and targeted <jats:italic>DPYD<\/jats:italic> genotyping (*2A, *13, D949V, *7) analyzed at Eurofins Biomnis (2015\u20132022).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2024-0317_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mean U was 9.9\u00a0\u00b1\u00a010.1\u202fng\/mL (median 8.7, range 1.6\u2013856). According to French recommendations, 7.3\u202f% of patients were partially deficient (U 16\u2013150\u202fng\/mL) and 0.02\u202f% completely deficient (U\u2265150\u202fng\/mL). <jats:italic>DPYD<\/jats:italic> variant frequencies were *2A: 0.83\u202f%, *13: 0.17\u202f%, D949V: 1.16\u202f%, *7: 0.05\u202f% (2 homozygous patients with U at 22 and 856\u202fng\/mL). Variant carriers exhibited higher U (median 13.8 vs. 8.6\u202fng\/mL), and lower UH2\/U (median 7.2 vs. 11.8) and UH2\/U<jats:sup>2<\/jats:sup> (median 0.54 vs. 1.37) relative to wild-type patients (p&lt;0.00001). Sixty-six% of variant carriers exhibited uracilemia &lt;16\u202fng\/mL, challenging correct identification of DPD deficiency based on U. The sensitivity (% patients with a deficient phenotype among variant carriers) of U threshold at 16\u202fng\/mL was 34\u202f%. The best discriminant marker for identifying variant carriers was UH2\/U<jats:sup>2<\/jats:sup>. UH2\/U<jats:sup>2<\/jats:sup>&lt;0.942 (29.7\u202f% of patients) showed enhanced sensitivity (81\u202f%) in identifying deleterious genotypes across different variants compared to 16\u202fng\/mL U.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2024-0317_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results reaffirm the poor concordance between DPD phenotyping and genotyping, suggesting that both approaches may be complementary and that targeted <jats:italic>DPYD<\/jats:italic> genotyping is not sufficiently reliable to identify all patients with complete deficiency.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2024-0317","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T06:32:16Z","timestamp":1718778736000},"page":"2415-2424","source":"Crossref","is-referenced-by-count":7,"title":["Can we identify patients carrying targeted deleterious <i>DPYD<\/i> variants with plasma uracil and dihydrouracil? A GPCO-RNPGx retrospective analysis"],"prefix":"10.1515","volume":"62","author":[{"given":"Manon","family":"Launay","sequence":"first","affiliation":[{"name":"Service de m\u00e9decine intensive et r\u00e9animation m\u00e9dicale et Centre R\u00e9gional de Pharmacovigilance , CHU de Saint-Etienne , Saint-Etienne , France"},{"name":"French Clinical Oncopharmacology Group (GPCO)-UNICANCER , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Raymond","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique , Laboratoire Eurofins Biomnis , Lyon , France"},{"name":"Francophone Network of Pharmacogenetics (RNPGx) , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Guitton","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie et Toxicologie, Centre Hospitalier Lyon-Sud , Hospices Civils de Lyon , Pierre-B\u00e9nite , France"},{"name":"Laboratoire de Toxicologie, ISPB, Facult\u00e9 de Pharmacie , Universit\u00e9 Lyon 1, Universit\u00e9 de Lyon , Lyon , France"},{"name":"French Clinical Oncopharmacology Group (GPCO)-UNICANCER , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Anne","family":"Loriot","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry , H\u00f4pital europ\u00e9en Georges-Pompidou, Assistance Publique H\u00f4pitaux de Paris-Centre , Paris , France"},{"name":"INSERM UMR-S1138, Universit\u00e9 of Paris Cit\u00e9, Centre de recherches des Cordeliers , Paris , France"},{"name":"Francophone Network of Pharmacogenetics (RNPGx) , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Chatelut","sequence":"additional","affiliation":[{"name":"Oncopole Claudius Regaud, Institut Universitaire du Cancer and CRCT , University of Toulouse, Inserm , Toulouse , France"},{"name":"French Clinical Oncopharmacology Group (GPCO)-UNICANCER , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Haufroid","sequence":"additional","affiliation":[{"name":"Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de recherche exp\u00e9rimentale et clinique, UClouvain, Brussels and Clinical Chemistry Department , Cliniques Universitaires Saint-Luc , Brussels , Belgium"},{"name":"Francophone Network of Pharmacogenetics (RNPGx) , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9886-412X","authenticated-orcid":false,"given":"Fabienne","family":"Thomas","sequence":"additional","affiliation":[{"name":"Oncopole Claudius Regaud, Institut Universitaire du Cancer and CRCT , University of Toulouse, Inserm , Toulouse , France"},{"name":"French Clinical Oncopharmacology Group (GPCO)-UNICANCER , Paris , France"},{"name":"Francophone Network of Pharmacogenetics (RNPGx) , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Etienne-Grimaldi","sequence":"additional","affiliation":[{"name":"Oncopharmacology Laboratory , Centre Antoine Lacassagne , Nice , France"},{"name":"French Clinical Oncopharmacology Group (GPCO)-UNICANCER , Paris , France"},{"name":"Francophone Network of Pharmacogenetics (RNPGx) , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"2024101207143216907_j_cclm-2024-0317_ref_001","doi-asserted-by":"crossref","unstructured":"Grothey, A, Sobrero, AF, Shields, AF, Yoshino, T, Paul, J, Taieb, J, et al.. 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Acta Oncol 2022;61:1400\u20135. https:\/\/doi.org\/10.1080\/0284186x.2022.2132117.","DOI":"10.1080\/0284186X.2022.2132117"},{"key":"2024101207143216907_j_cclm-2024-0317_ref_010","doi-asserted-by":"crossref","unstructured":"Laures, N, Konecki, C, Brugel, M, Giffard, A-L, Abdelli, N, Botsen, D, et al.. Impact of guidelines regarding dihydropyrimidine dehydrogenase (DPD) deficiency screening using uracil-based phenotyping on the reduction of severe side effect of 5-fluorouracil-based chemotherapy: a propension score analysis. Pharmaceutics 2022;14:2119. https:\/\/doi.org\/10.3390\/pharmaceutics14102119.","DOI":"10.3390\/pharmaceutics14102119"},{"key":"2024101207143216907_j_cclm-2024-0317_ref_011","doi-asserted-by":"crossref","unstructured":"Thomas, F, Launay, M, Guitton, J, Loriot, M-A, Boyer, J-C, Haufroid, V, et al.. Plasma uracil as a DPD phenotyping test: pre-analytical handling matters. 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Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency. Br J Clin Pharmacol 2023;89:762\u201372. https:\/\/doi.org\/10.1111\/bcp.15536.","DOI":"10.1111\/bcp.15536"},{"key":"2024101207143216907_j_cclm-2024-0317_ref_018","doi-asserted-by":"crossref","unstructured":"Loison, G, Bouges Le Royer, H, Marsili, S, Brice, A, Vintejoux, J, Yakoubi, M, et al.. Impact of hemolysis on uracilemia in the context of dihydropyrimidine dehydrogenase deficiency testing. Clin Chem Lab Med 2024;62:e129\u201331. https:\/\/doi.org\/10.1515\/cclm-2023-1096.","DOI":"10.1515\/cclm-2023-1096"},{"key":"2024101207143216907_j_cclm-2024-0317_ref_019","doi-asserted-by":"crossref","unstructured":"Thomas, F, Maillard, M, Launay, M, Tron, C, Etienne-Grimaldi, M-C, Gautier-Veyret, E, et al.. Artificial increase of uracilemia during fluoropyrimidine treatment can lead to DPD deficiency misinterpretation. 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