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

Autor:	Mirjam E. van de Velde, Aniek Uittenboogaard, Wenjian Yang, Erik Bonten, Cheng Cheng, Deqing Pei, Marleen H. van den Berg, Inge M. van der Sluis, Cor van den Bos, Floor C. H. Abbink, Marry M. van den Heuvel-Eibrink, Heidi Segers, Christophe Chantrain, Jutte van der Werff ten Bosch, Leen Willems, William E. Evans, Gertjan J. L. Kaspers
Přispěvatelé:	Clinical sciences, Growth and Development, Paediatric Oncology, Pediatrics, CCA - Cancer biology and immunology
Rok vydání:	2022
Předmět:	Cancer Research area under the curve VARIANT FGD4 CHILDREN vincristine neurotoxicity PLINK Pediatrics Perinatology and Child Health whole-exome sequencing children cancer toxicity DNA single-nucleotide polymorphism maximum concentration Children Cancer MARIE-TOOTH DISEASE Science & Technology hematology MUTATIONS NDRG1 CANCER Oncology NEUROTOXICITY Whole-exome sequencing oncology Life Sciences & Biomedicine
Zdroj:	Cancers; Volume 14; Issue 14; Pages: 3510 Cancers, 14(14):3510. Multidisciplinary Digital Publishing Institute (MDPI) van de Velde, M E, Uittenboogaard, A, Yang, W, Bonten, E, Cheng, C, Pei, D, van den Berg, M H, van der Sluis, I M, van den Bos, C, Abbink, F C H, van den Heuvel-Eibrink, M M, Segers, H, Chantrain, C, van der Werff ten Bosch, J, Willems, L, Evans, W E & Kaspers, G J L 2022, ' Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients ', Cancers, vol. 14, no. 14, 3510 . https://doi.org/10.3390/cancers14143510
ISSN:	2072-6694
Popis:	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. ispartof: CANCERS vol:14 issue:14 ispartof: location:Switzerland status: published
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7cf2606b06ed8365ca7f44d2297b555b https://pubmed.ncbi.nlm.nih.gov/35884569 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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