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- Title
Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors.
- Authors
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
- Abstract
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.
- Subjects
BRAIN tumors; WECHSLER Intelligence Scale for Children; RADIOTHERAPY safety; DNA analysis; SINGLE nucleotide polymorphisms; WECHSLER Adult Intelligence Scale; INTELLIGENCE tests
- Publication
Journal of Neuro-Oncology, 2023, Vol 165, Issue 1, p161
- ISSN
0167-594X
- Publication type
Article
- DOI
10.1007/s11060-023-04472-7