Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients.

DNA area under the curve cancer children maximum concentration neurotoxicity single-nucleotide polymorphism toxicity vincristine whole-exome sequencing

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
19 Jul 2022
Historique:
received: 13 05 2022
revised: 11 07 2022
accepted: 14 07 2022
entrez: 27 7 2022
pubmed: 28 7 2022
medline: 28 7 2022
Statut: epublish

Résumé

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-trait 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.

Identifiants

pubmed: 35884569
pii: cancers14143510
doi: 10.3390/cancers14143510
pmc: PMC9321338
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Netherlands Organization for Health and Development (program Proper Use of Medication)
ID : 836021006
Organisme : Belgian Health Care Knowledge Centre
ID : 16015
Organisme : Fulbright, the Netherlands
Organisme : Cancer Center Amsterdam
Organisme : René Vogels Foundation
Organisme : Ter Meulen Grant by the Academy Medical Sciences Fund

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Auteurs

Mirjam E van de Velde (ME)

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1081 HV Amsterdam, The Netherlands.
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Aniek Uittenboogaard (A)

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1081 HV Amsterdam, The Netherlands.
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.

Wenjian Yang (W)

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Erik Bonten (E)

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Cheng Cheng (C)

Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Deqing Pei (D)

Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Marleen H van den Berg (MH)

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1081 HV Amsterdam, The Netherlands.

Inge M van der Sluis (IM)

Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.

Cor van den Bos (C)

Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.
Emma Children's Hospital, Amsterdam UMC, Amsterdam Medical Center, Pediatric Oncology, 1105 Amsterdam, The Netherlands.

Floor C H Abbink (FCH)

Emma Children's Hospital, Amsterdam UMC, Amsterdam Medical Center, Pediatric Oncology, 1105 Amsterdam, The Netherlands.

Marry M van den Heuvel-Eibrink (MM)

Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.

Heidi Segers (H)

Department of Pediatric Hemato-Oncology, University Hospitals Leuven and Catholic University Leuven, 3000 Leuven, Belgium.

Christophe Chantrain (C)

Department of Pediatrics, Clinique du MontLégia, CHC, 4000 Liège, Belgium.

Jutte van der Werff Ten Bosch (J)

Department of Pediatric Onco-Hematology, Universitair Ziekenhuis Brussel, 1090 Brussels, Belgium.

Leen Willems (L)

Department of Paediatric Haematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, 9000 Ghent, Belgium.

William E Evans (WE)

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Gertjan J L Kaspers (GJL)

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1081 HV Amsterdam, The Netherlands.
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.

Classifications MeSH