{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:50:44Z","timestamp":1783612244329,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Netherlands Organization for Health and Development","award":["836021006"],"award-info":[{"award-number":["836021006"]}]},{"name":"Netherlands Organization for Health and Development","award":["16015"],"award-info":[{"award-number":["16015"]}]},{"DOI":"10.13039\/501100019353","name":"Belgian Health Care Knowledge Centre","doi-asserted-by":"publisher","award":["836021006"],"award-info":[{"award-number":["836021006"]}],"id":[{"id":"10.13039\/501100019353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019353","name":"Belgian Health Care Knowledge Centre","doi-asserted-by":"publisher","award":["16015"],"award-info":[{"award-number":["16015"]}],"id":[{"id":"10.13039\/501100019353","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fulbright in the Netherlands","award":["836021006"],"award-info":[{"award-number":["836021006"]}]},{"name":"Fulbright in the Netherlands","award":["16015"],"award-info":[{"award-number":["16015"]}]},{"name":"Cancer Center Amsterdam","award":["836021006"],"award-info":[{"award-number":["836021006"]}]},{"name":"Cancer Center Amsterdam","award":["16015"],"award-info":[{"award-number":["16015"]}]},{"name":"Ren\u00e9 Vogels Foundation","award":["836021006"],"award-info":[{"award-number":["836021006"]}]},{"name":"Ren\u00e9 Vogels Foundation","award":["16015"],"award-info":[{"award-number":["16015"]}]},{"name":"Academy Medical Sciences Fund","award":["836021006"],"award-info":[{"award-number":["836021006"]}]},{"name":"Academy Medical Sciences Fund","award":["16015"],"award-info":[{"award-number":["16015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occasions at multiple time points. A linear two-compartment model with first-order elimination was used, and targeted next-generation DNA sequencing was performed. Genotype\u2013trait associations were analyzed using mixed-effect models or logistic regression analysis for repeated measures, or Poisson regression analysis in which the highest VIPN score per patient was included. Nine single-nucleotide polymorphisms (SNPs) in seven genes (NDRG1, GARS, FIG4, FGD4, SEPTIN9, CEP72, and ETAA1) were associated with VIPN. Furthermore, three SNPs in three genes (MTNR1B, RAB7A and SNU13) were associated with PK of VCR. In conclusion, PK of VCR and VIPN are influenced by SNPs; upfront identification of those that lead to an altered susceptibility to VIPN or VCR exposure could help individualize VCR treatment.<\/jats:p>","DOI":"10.3390\/cancers14143510","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T23:10:22Z","timestamp":1658272222000},"page":"3510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0424-2085","authenticated-orcid":false,"given":"Mirjam E.","family":"van de Velde","sequence":"first","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-8177","authenticated-orcid":false,"given":"Aniek","family":"Uittenboogaard","sequence":"additional","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Bonten","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deqing","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen H.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge M.","family":"van der Sluis","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cor","family":"van den Bos","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"},{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam Medical Center, Pediatric Oncology, 1105 Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor C. H.","family":"Abbink","sequence":"additional","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, Amsterdam Medical Center, Pediatric Oncology, 1105 Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marry M.","family":"van den Heuvel-Eibrink","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-7850","authenticated-orcid":false,"given":"Heidi","family":"Segers","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, University Hospitals Leuven and Catholic University Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Chantrain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinique du MontL\u00e9gia, CHC, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutte","family":"van der Werff ten Bosch","sequence":"additional","affiliation":[{"name":"Department of Pediatric Onco-Hematology, Universitair Ziekenhuis Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen","family":"Willems","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-8475","authenticated-orcid":false,"given":"Gertjan J. L.","family":"Kaspers","sequence":"additional","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S1040-8428(98)00023-7","article-title":"Vincristine revisited","volume":"29","author":"Gidding","year":"1999","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.critrevonc.2017.04.004","article-title":"Vincristine-induced peripheral neuropathy in children with cancer: A systematic review","volume":"114","author":"Kaspers","year":"2017","journal-title":"Crit. Rev. Oncol. 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