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03.01.2019 | Laboratory Investigation

PPAR and GST polymorphisms may predict changes in intellectual functioning in medulloblastoma survivors

verfasst von: Adeoye Oyefiade, Lauren Erdman, Anna Goldenberg, David Malkin, Eric Bouffet, Michael D. Taylor, Vijay Ramaswamy, Nadia Scantlebury, Nicole Law, Donald J. Mabbott

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2019

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Abstract

Purpose

Advances in the treatment of pediatric medulloblastoma have led to improved survival rates, though treatment-related toxicity leaves children with significant long-term deficits. There is significant variability in the cognitive outcome of medulloblastoma survivors, and it has been suggested that this variability may be attributable to genetic factors. The aim of this study was to explore the contributions of single nucleotide polymorphisms (SNPs) in two genes, peroxisome proliferator activated receptor (PPAR) and glutathione-S-transferase (GST), to changes in general intellectual functioning in medulloblastoma survivors.

Methods

Patients (n = 44, mean_age = 6.71 years, 61.3% males) were selected on the basis of available tissue samples and neurocognitive measures. Patients received surgical tumor resection, craniospinal radiation, radiation boost to the tumor site, and multiagent chemotherapy. Genotyping analyses were completed using the Illumina Human Omni2.5 BeadChip, and 41 single nucleotide polymorphisms (SNPs) were assessed across both genes. We used a machine learning algorithm to identify polymorphisms that were significantly associated with declines in general intellectual functioning following treatment for medulloblastoma.

Results

We identified age at diagnosis, radiation therapy, chemotherapy, and eight SNPs associated with PPARs as predictors of general intellectual functioning. Of the eight SNPs identified, PPARα (rs6008197), PPARγ (rs13306747), and PPARδ (rs3734254) were most significantly associated with long-term changes in general intellectual functioning in medulloblastoma survivors.

Conclusions

PPAR polymorphisms may predict intellectual outcome changes in children treated for medulloblastoma. Importantly, emerging evidence suggests that PPAR agonists may provide an opportunity to minimize the effects of treatment-related cognitive sequelae in these children.

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Titel: PPAR and GST polymorphisms may predict changes in intellectual functioning in medulloblastoma survivors
verfasst von: Adeoye Oyefiade
Lauren Erdman
Anna Goldenberg
David Malkin
Eric Bouffet
Michael D. Taylor
Vijay Ramaswamy
Nadia Scantlebury
Nicole Law
Donald J. Mabbott
Publikationsdatum: 03.01.2019
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2019
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-03083-x

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PPAR and GST polymorphisms may predict changes in intellectual functioning in medulloblastoma survivors

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

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Conclusions

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