{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:12:02Z","timestamp":1792761122203,"version":"4.5.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Transl Oncol"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping <jats:italic>DPYD<\/jats:italic> gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and\/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of <jats:italic>DPYD<\/jats:italic> previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.<\/jats:p>","DOI":"10.1007\/s12094-021-02708-4","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T10:02:23Z","timestamp":1636797743000},"page":"483-494","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-9978","authenticated-orcid":false,"given":"P.","family":"Garc\u00eda-Alfonso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1660-3135","authenticated-orcid":false,"given":"M.","family":"Saiz-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Mond\u00e9jar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"P\u00e1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8584-3263","authenticated-orcid":false,"given":"A. M.","family":"Borobia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Safont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Colomer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Garc\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Herrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. A.","family":"L\u00f3pez-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6519-8885","authenticated-orcid":false,"given":"F.","family":"Abad-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"issue":"2","key":"2708_CR1","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1002\/cpt.911","volume":"103","author":"U Amstutz","year":"2018","unstructured":"Amstutz U, Henricks LM, Offer SM, Barbarino J, Schellens JHM, Swen JJ, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update. Clin Pharmacol Ther. 2018;103(2):210\u20136. https:\/\/doi.org\/10.1002\/cpt.911.","journal-title":"Clin Pharmacol Ther"},{"issue":"4","key":"2708_CR2","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41431-019-0540-0","volume":"28","author":"C Lunenburg","year":"2020","unstructured":"Lunenburg C, van der Wouden CH, Nijenhuis M, Crommentuijn-van Rhenen MH, de Boer-Veger NJ, Buunk AM, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines. Eur J Hum Genet EJHG. 2020;28(4):508\u201317. https:\/\/doi.org\/10.1038\/s41431-019-0540-0.","journal-title":"Eur J Hum Genet EJHG"},{"key":"2708_CR3","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju298","author":"AM Lee","year":"2014","unstructured":"Lee AM, Shi Q, Pavey E, Alberts SR, Sargent DJ, Sinicrope FA, et al. DPYD variants as predictors of 5-fluorouracil toxicity in adjuvant colon cancer treatment (NCCTG N0147). J Natl Cancer Inst. 2014. https:\/\/doi.org\/10.1093\/jnci\/dju298.","journal-title":"J Natl Cancer Inst"},{"issue":"3","key":"2708_CR4","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1002\/ijc.29025","volume":"136","author":"TK Froehlich","year":"2015","unstructured":"Froehlich TK, Amstutz U, Aebi S, Joerger M, Largiad\u00e8r CR. Clinical importance of risk variants in the dihydropyrimidine dehydrogenase gene for the prediction of early-onset fluoropyrimidine toxicity. Int J Cancer. 2015;136(3):730\u20139. https:\/\/doi.org\/10.1002\/ijc.29025.","journal-title":"Int J Cancer"},{"issue":"16","key":"2708_CR5","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1016\/s1470-2045(15)00286-7","volume":"16","author":"D Meulendijks","year":"2015","unstructured":"Meulendijks D, Henricks LM, Sonke GS, Deenen MJ, Froehlich TK, Amstutz U, et al. Clinical relevance of DPYD variants c.1679T>G, c.1236G>A\/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 2015;16(16):1639\u201350. https:\/\/doi.org\/10.1016\/s1470-2045(15)00286-7.","journal-title":"Lancet Oncol"},{"issue":"11","key":"2708_CR6","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/s1470-2045(18)30686-7","volume":"19","author":"LM Henricks","year":"2018","unstructured":"Henricks LM, Lunenburg C, de Man FM, Meulendijks D, Frederix GWJ, Kienhuis E, et al. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol. 2018;19(11):1459\u201367. https:\/\/doi.org\/10.1016\/s1470-2045(18)30686-7.","journal-title":"Lancet Oncol"},{"issue":"6","key":"2708_CR7","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/clpt.2013.172","volume":"94","author":"KE Caudle","year":"2013","unstructured":"Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. 2013;94(6):640\u20135. https:\/\/doi.org\/10.1038\/clpt.2013.172.","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"2708_CR8","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1053\/j.seminoncol.2017.02.008","volume":"44","author":"M Boisdron-Celle","year":"2017","unstructured":"Boisdron-Celle M, Capitain O, Faroux R, Borg C, Metges JP, Galais MP, et al. Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: assessment of a multiparametric approach. Semin Oncol. 2017;44(1):13\u201323. https:\/\/doi.org\/10.1053\/j.seminoncol.2017.02.008.","journal-title":"Semin Oncol"},{"key":"2708_CR9","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12981","author":"TJ Wigle","year":"2021","unstructured":"Wigle TJ, Povitz BL, Medwid S, Teft WA, Legan RM, Lenehan J, et al. Impact of pretreatment dihydropyrimidine dehydrogenase genotype-guided fluoropyrimidine dosing on chemotherapy associated adverse events. Clin Transl Sci. 2021. https:\/\/doi.org\/10.1111\/cts.12981.","journal-title":"Clin Transl Sci"},{"key":"2708_CR10","unstructured":"Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios. Fluorouracilo, capecitabina, tegafur y flucitosina en pacientes con d\u00e9ficit de dihidropirimidina deshidrogenasa. 2020. https:\/\/www.aemps.gob.es\/informa\/notasinformativas\/medicamentosusohumano-3\/seguridad-1\/2020-seguridad-1\/fluorouracilo-capecitabina-tegafur-y-flucitosina-en-pacientes-con-deficit-de-dihidropirimidina-deshidrogenasa. 201."},{"key":"2708_CR11","unstructured":"Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios. Ficha t\u00e9cnica de 5 Fluorouracilo Accord. 2020. https:\/\/cima.aemps.es\/cima\/dochtml\/ft\/71868\/FT_71868.html."},{"key":"2708_CR12","unstructured":"Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios. Ficha t\u00e9cnica de Xeloda (capecitabina). https:\/\/cima.aemps.es\/cima\/dochtml\/ft\/00163002\/FT_00163002.html."},{"key":"2708_CR13","unstructured":"Ram\u00edrez Ruda CA, Garc\u00eda Paredes B, Sastre Valera J. Antimetabolitos (I). Oncomecum: Permanyer; 2015."},{"key":"2708_CR14","unstructured":"Manzano Fern\u00e1ndez A, Aguado de la Rosa C. Esquemas m\u00e1s habituales en oncolog\u00eda. Oncomecum: Permanyer; 2015."},{"key":"2708_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107447","volume":"206","author":"S Vodenkova","year":"2020","unstructured":"Vodenkova S, Buchler T, Cervena K, Veskrnova V, Vodicka P, Vymetalkova V. 5-fluorouracil and other fluoropyrimidines in colorectal cancer: past, present and future. Pharmacol Ther. 2020;206: 107447. https:\/\/doi.org\/10.1016\/j.pharmthera.2019.107447.","journal-title":"Pharmacol Ther"},{"issue":"5","key":"2708_CR16","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1517\/14740338.2010.511610","volume":"9","author":"SE Mikhail","year":"2010","unstructured":"Mikhail SE, Sun JF, Marshall JL. Safety of capecitabine: a review. Expert Opin Drug Saf. 2010;9(5):831\u201341. https:\/\/doi.org\/10.1517\/14740338.2010.511610.","journal-title":"Expert Opin Drug Saf"},{"issue":"21","key":"2708_CR17","doi-asserted-by":"publisher","first-page":"4097","DOI":"10.1200\/jco.2001.19.21.4097","volume":"19","author":"E Van Cutsem","year":"2001","unstructured":"Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol Off J Am Soc Clin Oncol. 2001;19(21):4097\u2013106. https:\/\/doi.org\/10.1200\/jco.2001.19.21.4097.","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"issue":"1","key":"2708_CR18","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1159\/000180580","volume":"16","author":"DW Cockcroft","year":"1976","unstructured":"Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31\u201341. https:\/\/doi.org\/10.1159\/000180580.","journal-title":"Nephron"},{"issue":"4","key":"2708_CR19","doi-asserted-by":"publisher","first-page":"215","DOI":"10.2165\/00003088-198916040-00002","volume":"16","author":"RB Diasio","year":"1989","unstructured":"Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989;16(4):215\u201337. https:\/\/doi.org\/10.2165\/00003088-198916040-00002.","journal-title":"Clin Pharmacokinet"},{"issue":"12","key":"2708_CR20","first-page":"4363","volume":"9","author":"AB van Kuilenburg","year":"2003","unstructured":"van Kuilenburg AB, Meinsma R, Zonnenberg BA, Zoetekouw L, Baas F, Matsuda K, et al. Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity. Clin Cancer Res Off J Am Assoc Cancer Res. 2003;9(12):4363\u20137.","journal-title":"Clin Cancer Res Off J Am Assoc Cancer Res"},{"issue":"4","key":"2708_CR21","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1097\/FPC.0b013e32833c6107","volume":"21","author":"CF Thorn","year":"2011","unstructured":"Thorn CF, Marsh S, Carrillo MW, McLeod HL, Klein TE, Altman RB. PharmGKB summary: fluoropyrimidine pathways. Pharmacogenet Genomics. 2011;21(4):237\u201342. https:\/\/doi.org\/10.1097\/FPC.0b013e32833c6107.","journal-title":"Pharmacogenet Genomics"},{"issue":"4","key":"2708_CR22","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1093\/jnci\/djaa124","volume":"113","author":"AD Wagner","year":"2021","unstructured":"Wagner AD, Grothey A, Andre T, Dixon JG, Wolmark N, Haller DG, et al. Sex and adverse events of adjuvant chemotherapy in colon cancer: an analysis of 34 640 patients in the ACCENT database. J Natl Cancer Inst. 2021;113(4):400\u20137. https:\/\/doi.org\/10.1093\/jnci\/djaa124.","journal-title":"J Natl Cancer Inst"},{"issue":"8","key":"2708_CR23","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1016\/s0959-8049(98)00058-6","volume":"34","author":"M Miwa","year":"1998","unstructured":"Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer (Oxf, Engl). 1998;34(8):1274\u201381. https:\/\/doi.org\/10.1016\/s0959-8049(98)00058-6.","journal-title":"Eur J Cancer (Oxf, Engl)"},{"issue":"3","key":"2708_CR24","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1006\/geno.1998.5379","volume":"51","author":"X Wei","year":"1998","unstructured":"Wei X, Elizondo G, Sapone A, McLeod HL, Raunio H, Fernandez-Salguero P, et al. Characterization of the human dihydropyrimidine dehydrogenase gene. Genomics. 1998;51(3):391\u2013400. https:\/\/doi.org\/10.1006\/geno.1998.5379.","journal-title":"Genomics"},{"issue":"7","key":"2708_CR25","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.ejca.2003.12.004","volume":"40","author":"AB van Kuilenburg","year":"2004","unstructured":"van Kuilenburg AB. Dihydropyrimidine dehydrogenase and the efficacy and toxicity of 5-fluorouracil. Eur J Cancer (Oxf, Engl). 2004;40(7):939\u201350. https:\/\/doi.org\/10.1016\/j.ejca.2003.12.004.","journal-title":"Eur J Cancer (Oxf, Engl)"},{"key":"2708_CR26","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/s0065-2571(00)00011-x","volume":"41","author":"MR Johnson","year":"2001","unstructured":"Johnson MR, Diasio RB. Importance of dihydropyrimidine dehydrogenase (DPD) deficiency in patients exhibiting toxicity following treatment with 5-fluorouracil. Adv Enzyme Regul. 2001;41:151\u20137. https:\/\/doi.org\/10.1016\/s0065-2571(00)00011-x.","journal-title":"Adv Enzyme Regul"},{"issue":"11","key":"2708_CR27","doi-asserted-by":"publisher","first-page":"2895","DOI":"10.1158\/1535-7163.mct-06-0327","volume":"5","author":"A Morel","year":"2006","unstructured":"Morel A, Boisdron-Celle M, Fey L, Soulie P, Craipeau MC, Traore S, et al. Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther. 2006;5(11):2895\u2013904. https:\/\/doi.org\/10.1158\/1535-7163.mct-06-0327.","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"2708_CR28","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1172\/jci113308","volume":"81","author":"RB Diasio","year":"1988","unstructured":"Diasio RB, Beavers TL, Carpenter JT. Familial deficiency of dihydropyrimidine dehydrogenase Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. J Clin Invest. 1988;81(1):47\u201351. https:\/\/doi.org\/10.1172\/jci113308.","journal-title":"J Clin Invest"},{"key":"2708_CR29","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/978-1-4615-5381-6_58","volume":"431","author":"AB Van Kuilenburg","year":"1998","unstructured":"Van Kuilenburg AB, Vreken P, Beex LV, Meinsma R, Van Lenthe H, De Abreu RA, et al. Heterozygosity for a point mutation in an invariant splice donor site of dihydropyrimidine dehydrogenase and severe 5-fluorouracil related toxicity. Adv Exp Med Biol. 1998;431:293\u20138. https:\/\/doi.org\/10.1007\/978-1-4615-5381-6_58.","journal-title":"Adv Exp Med Biol"},{"issue":"Pt 1","key":"2708_CR30","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1042\/bj3640157","volume":"364","author":"AB van Kuilenburg","year":"2002","unstructured":"van Kuilenburg AB, Dobritzsch D, Meinsma R, Haasjes J, Waterham HR, Nowaczyk MJ, et al. Novel disease-causing mutations in the dihydropyrimidine dehydrogenase gene interpreted by analysis of the three-dimensional protein structure. Biochem J. 2002;364(Pt 1):157\u201363. https:\/\/doi.org\/10.1042\/bj3640157.","journal-title":"Biochem J"},{"issue":"D1","key":"2708_CR31","doi-asserted-by":"publisher","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","volume":"46","author":"MJ Landrum","year":"2018","unstructured":"Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46(D1):D1062\u20137. https:\/\/doi.org\/10.1093\/nar\/gkx1153.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"2708_CR32","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1002\/cpt.685","volume":"102","author":"Q Nie","year":"2017","unstructured":"Nie Q, Shrestha S, Tapper EE, Trogstad-Isaacson CS, Bouchonville KJ, Lee AM, et al. Quantitative contribution of rs75017182 to dihydropyrimidine dehydrogenase mrna splicing and enzyme activity. Clin Pharmacol Ther. 2017;102(4):662\u201370. https:\/\/doi.org\/10.1002\/cpt.685.","journal-title":"Clin Pharmacol Ther"},{"issue":"7571","key":"2708_CR33","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68\u201374. https:\/\/doi.org\/10.1038\/nature15393.","journal-title":"Nature"},{"key":"2708_CR34","unstructured":"Ensembl Data. DPYD rs55886062. https:\/\/www.ensembl.org\/Homo_sapiens\/Variation\/Population?db=core;r=1:97515287-97516287;v=rs55886062;vdb=variation;vf=7116226."},{"key":"2708_CR35","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2350","author":"M Whirl-Carrillo","year":"2021","unstructured":"Whirl-Carrillo M, Huddart R, Gong L, Sangkuhl K, Thorn CF, Whaley R, et al. An evidence-based framework for evaluating pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2021. https:\/\/doi.org\/10.1002\/cpt.2350.","journal-title":"Clin Pharmacol Ther"},{"issue":"4","key":"2708_CR36","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/clpt.2012.96","volume":"92","author":"M Whirl-Carrillo","year":"2012","unstructured":"Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012;92(4):414\u20137. https:\/\/doi.org\/10.1038\/clpt.2012.96.","journal-title":"Clin Pharmacol Ther"},{"key":"2708_CR37","unstructured":"Rehm H, Daly MJ. gnomAD v 2.1.1\u2014DPYD dihydropyrimidine dehydrogenase. https:\/\/gnomad.broadinstitute.org\/gene\/ENSG00000188641?dataset=gnomad_r2_1."},{"key":"2708_CR38","unstructured":"Consortium CPI. DPYD allele functionality table. CPIC\u00ae Guideline for Fluoropyrimidines and DPYD. https:\/\/cpicpgx.org\/guidelines\/guideline-for-fluoropyrimidines-and-dpyd\/."},{"issue":"5","key":"2708_CR39","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1001\/jamaoncol.2015.5392","volume":"2","author":"V Boige","year":"2016","unstructured":"Boige V, Vincent M, Alexandre P, Tejpar S, Landolfi S, Le Malicot K, et al. DPYD genotyping to predict adverse events following treatment with fluorouracil-based adjuvant chemotherapy in patients with stage III colon cancer: a secondary analysis of the PETACC-8 randomized clinical trial. JAMA Oncol. 2016;2(5):655\u201362. https:\/\/doi.org\/10.1001\/jamaoncol.2015.5392.","journal-title":"JAMA Oncol"},{"issue":"10","key":"2708_CR40","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1200\/jco.2013.51.1857","volume":"32","author":"D Rosmarin","year":"2014","unstructured":"Rosmarin D, Palles C, Church D, Domingo E, Jones A, Johnstone E, et al. Genetic markers of toxicity from capecitabine and other fluorouracil-based regimens: investigation in the QUASAR2 study, systematic review, and meta-analysis. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32(10):1031\u20139. https:\/\/doi.org\/10.1200\/jco.2013.51.1857.","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"issue":"3","key":"2708_CR41","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1111\/j.1365-2710.2008.00898.x","volume":"33","author":"YF He","year":"2008","unstructured":"He YF, Wei W, Zhang X, Li YH, Li S, Wang FH, et al. Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in Chinese cancer patients. J Clin Pharm Ther. 2008;33(3):307\u201314. https:\/\/doi.org\/10.1111\/j.1365-2710.2008.00898.x.","journal-title":"J Clin Pharm Ther"},{"issue":"3","key":"2708_CR42","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.bbadis.2016.12.010","volume":"1863","author":"AB van Kuilenburg","year":"2017","unstructured":"van Kuilenburg AB, Meijer J, Maurer D, Dobritzsch D, Meinsma R, Los M, et al. Severe fluoropyrimidine toxicity due to novel and rare DPYD missense mutations, deletion and genomic amplification affecting DPD activity and mRNA splicing. Biochim Biophys Acta. 2017;1863(3):721\u201330. https:\/\/doi.org\/10.1016\/j.bbadis.2016.12.010.","journal-title":"Biochim Biophys Acta"},{"key":"2708_CR43","doi-asserted-by":"publisher","first-page":"4517","DOI":"10.2147\/cmar.s174470","volume":"10","author":"X Garc\u00eda-Gonz\u00e1lez","year":"2018","unstructured":"Garc\u00eda-Gonz\u00e1lez X, L\u00f3pez-Tarruella S, Garc\u00eda MI, Gonz\u00e1lez-Haba E, Blanco C, Salvador-Martin S, et al. Severe toxicity to capecitabine due to a new variant at a donor splicing site in the dihydropyrimidine dehydrogenase (DPYD) gene. Cancer Manag Res. 2018;10:4517\u201322. https:\/\/doi.org\/10.2147\/cmar.s174470.","journal-title":"Cancer Manag Res"},{"key":"2708_CR44","unstructured":"Rodr\u00edguez-Antona C, Apellaniz M, Borobia A, Tar\u00f3n M, Gonz\u00e1lez-Neira A, Llenera A et al. Recomendaciones metodol\u00f3gicas y de interpretaci\u00f3n anal\u00edtica de la Sociedad Espa\u00f1ola de Farmacogen\u00e9tica y Farmacogen\u00f3mica para el testado del d\u00e9ficit de dihidropirimidina deshidrogenasa. 2021."},{"issue":"9","key":"2708_CR45","doi-asserted-by":"publisher","first-page":"979","DOI":"10.2217\/pgs-2016-0006","volume":"17","author":"L Cortejoso","year":"2016","unstructured":"Cortejoso L, Garc\u00eda-Gonz\u00e1lez X, Garc\u00eda MI, Garc\u00eda-Alfonso P, Sanjurjo M, L\u00f3pez-Fern\u00e1ndez LA. Cost-effectiveness of screening for DPYD polymorphisms to prevent neutropenia in cancer patients treated with fluoropyrimidines. Pharmacogenomics. 2016;17(9):979\u201384. https:\/\/doi.org\/10.2217\/pgs-2016-0006.","journal-title":"Pharmacogenomics"},{"key":"2708_CR46","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10120511","author":"V Hlavac","year":"2018","unstructured":"Hlavac V, Kovacova M, Elsnerova K, Brynychova V, Kozevnikovova R, Raus K, et al. Use of germline genetic variability for prediction of chemoresistance and prognosis of breast cancer patients. Cancers. 2018. https:\/\/doi.org\/10.3390\/cancers10120511.","journal-title":"Cancers"},{"issue":"1","key":"2708_CR47","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s00280-020-04093-1","volume":"86","author":"X Garc\u00eda-Gonz\u00e1lez","year":"2020","unstructured":"Garc\u00eda-Gonz\u00e1lez X, Kaczmarczyk B, Abarca-Zabal\u00eda J, Thomas F, Garc\u00eda-Alfonso P, Robles L, et al. New DPYD variants causing DPD deficiency in patients treated with fluoropyrimidine. Cancer Chemother Pharmacol. 2020;86(1):45\u201354. https:\/\/doi.org\/10.1007\/s00280-020-04093-1.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"3","key":"2708_CR48","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/cpt.2069","volume":"109","author":"JE Knikman","year":"2021","unstructured":"Knikman JE, Gelderblom H, Beijnen JH, Cats A, Guchelaar HJ, Henricks LM. Individualized dosing of fluoropyrimidine-based chemotherapy to prevent severe fluoropyrimidine-related toxicity: what are the options? Clin Pharmacol Ther. 2021;109(3):591\u2013604. https:\/\/doi.org\/10.1002\/cpt.2069.","journal-title":"Clin Pharmacol Ther"},{"issue":"11","key":"2708_CR49","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1159\/000510258","volume":"43","author":"B W\u00f6rmann","year":"2020","unstructured":"W\u00f6rmann B, Bokemeyer C, Burmeister T, K\u00f6hne CH, Schwab M, Arnold D, et al. Dihydropyrimidine dehydrogenase testing prior to treatment with 5-fluorouracil, capecitabine, and tegafur: a consensus paper. Oncol Res Treat. 2020;43(11):628\u201336. https:\/\/doi.org\/10.1159\/000510258.","journal-title":"Oncol Res Treat"},{"issue":"9","key":"2708_CR50","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1002\/ijc.32022","volume":"144","author":"LM Henricks","year":"2019","unstructured":"Henricks LM, van Merendonk LN, Meulendijks D, Deenen MJ, Beijnen JH, de Boer A, et al. Effectiveness and safety of reduced-dose fluoropyrimidine therapy in patients carrying the DPYD*2A variant: a matched pair analysis. Int J Cancer. 2019;144(9):2347\u201354. https:\/\/doi.org\/10.1002\/ijc.32022.","journal-title":"Int J Cancer"},{"issue":"3","key":"2708_CR51","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1200\/jco.2015.63.1325","volume":"34","author":"MJ Deenen","year":"2016","unstructured":"Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, et al. Upfront genotyping of DPYD*2A to individualize fluoropyrimidine therapy: a safety and cost analysis. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(3):227\u201334. https:\/\/doi.org\/10.1200\/jco.2015.63.1325.","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"2708_CR52","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.ejca.2018.11.010","volume":"107","author":"LM Henricks","year":"2019","unstructured":"Henricks LM, Lunenburg C, de Man FM, Meulendijks D, Frederix GWJ, Kienhuis E, et al. A cost analysis of upfront DPYD genotype-guided dose individualisation in fluoropyrimidine-based anticancer therapy. Eur J Cancer (Oxford, Engl). 2019;107:60\u20137. https:\/\/doi.org\/10.1016\/j.ejca.2018.11.010.","journal-title":"Eur J Cancer (Oxford, Engl)"},{"issue":"4","key":"2708_CR53","doi-asserted-by":"publisher","first-page":"155932581880304","DOI":"10.1177\/1559325818803042","volume":"16","author":"C Murphy","year":"2018","unstructured":"Murphy C, Byrne S, Ahmed G, Kenny A, Gallagher J, Harvey H, et al. Cost implications of reactive versus prospective testing for dihydropyrimidine dehydrogenase deficiency in patients with colorectal cancer: a single-institution experience. Dose Response Publ Int Hormesis Soc. 2018;16(4):1559325818803042. https:\/\/doi.org\/10.1177\/1559325818803042.","journal-title":"Dose Response Publ Int Hormesis Soc"},{"issue":"4","key":"2708_CR54","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1002\/cpt.1257","volume":"105","author":"G Toffoli","year":"2019","unstructured":"Toffoli G, Innocenti F, Polesel J, De Mattia E, Sartor F, Dalle Fratte C, et al. The genotype for DPYD risk variants in patients with colorectal cancer and the related toxicity management costs in clinical practice. Clin Pharmacol Ther. 2019;105(4):994\u20131002. https:\/\/doi.org\/10.1002\/cpt.1257.","journal-title":"Clin Pharmacol Ther"}],"container-title":["Clinical and Translational Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12094-021-02708-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12094-021-02708-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12094-021-02708-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T16:06:37Z","timestamp":1646064397000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12094-021-02708-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,13]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["2708"],"URL":"https:\/\/doi.org\/10.1007\/s12094-021-02708-4","relation":{},"ISSN":["1699-048X","1699-3055"],"issn-type":[{"value":"1699-048X","type":"print"},{"value":"1699-3055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,13]]},"assertion":[{"value":"27 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they do not have any conflict of interest related with this project.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"For this type of study informed consent is not required.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}