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Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors

BACKGROUND: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for treatment toxicity and adverse neurocognitive ou...

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Autores principales: Grob, Sydney T., Miller, Kristen R., Sanford, Bridget, Donson, Andrew M., Jones, Kenneth, Griesinger, Andrea M., Amani, Vladimir, Foreman, Nicholas K., Liu, Arthur, Handler, Michael, Hankinson, Todd C., Milgrom, Sarah, Levy, Jean M. Mulcahy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638163/
https://www.ncbi.nlm.nih.gov/pubmed/37878192
http://dx.doi.org/10.1007/s11060-023-04472-7
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author Grob, Sydney T.
Miller, Kristen R.
Sanford, Bridget
Donson, Andrew M.
Jones, Kenneth
Griesinger, Andrea M.
Amani, Vladimir
Foreman, Nicholas K.
Liu, Arthur
Handler, Michael
Hankinson, Todd C.
Milgrom, Sarah
Levy, Jean M. Mulcahy
author_facet Grob, Sydney T.
Miller, Kristen R.
Sanford, Bridget
Donson, Andrew M.
Jones, Kenneth
Griesinger, Andrea M.
Amani, Vladimir
Foreman, Nicholas K.
Liu, Arthur
Handler, Michael
Hankinson, Todd C.
Milgrom, Sarah
Levy, Jean M. Mulcahy
author_sort Grob, Sydney T.
collection PubMed
description BACKGROUND: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for treatment toxicity and adverse neurocognitive outcomes. MATERIALS: The Human 660W-Quad v1.0 DNA BeadChip analysis (Illumina) was used to evaluate 1048 SNPs from 59 DNA repair genes in 46 subjects. IQ testing was measured by the Wechsler Intelligence Scale for Children. Linear regression was used to identify the 10 SNPs with the strongest association with IQ scores while adjusting for radiation type. RESULTS: The low vs high IQ patient cohorts were well matched for time from first treatment to most recent IQ, first treatment age, sex, and treatments received. 5 SNPs on 3 different genes (CYP29, XRCC1, and BRCA1) and on 3 different chromosomes (10, 19, and 17) had the strongest association with most recent IQ score that was not modified by radiation type. Furthermore, 5 SNPs on 4 different genes (WRN, NR3C1, ERCC4, RAD51L1) on 4 different chromosomes (8, 5, 16, 14) had the strongest association with change in IQ independent of radiation type, first IQ, and years between IQ measures. CONCLUSIONS: SNPs offer the potential to predict adverse neurocognitive outcomes in pediatric brain tumor survivors. Our results require validation in a larger patient cohort. Improving the ability to identify children at risk of treatment related neurocognitive deficits could allow for better treatment stratification and early cognitive interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-023-04472-7.
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spelling pubmed-106381632023-11-14 Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors Grob, Sydney T. Miller, Kristen R. Sanford, Bridget Donson, Andrew M. Jones, Kenneth Griesinger, Andrea M. Amani, Vladimir Foreman, Nicholas K. Liu, Arthur Handler, Michael Hankinson, Todd C. Milgrom, Sarah Levy, Jean M. Mulcahy J Neurooncol Research BACKGROUND: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for treatment toxicity and adverse neurocognitive outcomes. MATERIALS: The Human 660W-Quad v1.0 DNA BeadChip analysis (Illumina) was used to evaluate 1048 SNPs from 59 DNA repair genes in 46 subjects. IQ testing was measured by the Wechsler Intelligence Scale for Children. Linear regression was used to identify the 10 SNPs with the strongest association with IQ scores while adjusting for radiation type. RESULTS: The low vs high IQ patient cohorts were well matched for time from first treatment to most recent IQ, first treatment age, sex, and treatments received. 5 SNPs on 3 different genes (CYP29, XRCC1, and BRCA1) and on 3 different chromosomes (10, 19, and 17) had the strongest association with most recent IQ score that was not modified by radiation type. Furthermore, 5 SNPs on 4 different genes (WRN, NR3C1, ERCC4, RAD51L1) on 4 different chromosomes (8, 5, 16, 14) had the strongest association with change in IQ independent of radiation type, first IQ, and years between IQ measures. CONCLUSIONS: SNPs offer the potential to predict adverse neurocognitive outcomes in pediatric brain tumor survivors. Our results require validation in a larger patient cohort. Improving the ability to identify children at risk of treatment related neurocognitive deficits could allow for better treatment stratification and early cognitive interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-023-04472-7. Springer US 2023-10-25 2023 /pmc/articles/PMC10638163/ /pubmed/37878192 http://dx.doi.org/10.1007/s11060-023-04472-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Grob, Sydney T.
Miller, Kristen R.
Sanford, Bridget
Donson, Andrew M.
Jones, Kenneth
Griesinger, Andrea M.
Amani, Vladimir
Foreman, Nicholas K.
Liu, Arthur
Handler, Michael
Hankinson, Todd C.
Milgrom, Sarah
Levy, Jean M. Mulcahy
Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors
title Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors
title_full Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors
title_fullStr Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors
title_full_unstemmed Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors
title_short Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors
title_sort genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638163/
https://www.ncbi.nlm.nih.gov/pubmed/37878192
http://dx.doi.org/10.1007/s11060-023-04472-7
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