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J Neurooncol. 2019 Mar;142(1):39-48. doi: 10.1007/s11060-018-03083-x. Epub 2019 Jan 3.

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

Author information

1
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada. ade.oyefiade@sickkids.ca.
2
Department of Psychology, University of Toronto, Toronto, ON, Canada. ade.oyefiade@sickkids.ca.
3
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
4
Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
5
Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
6
Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada.
7
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.
8
Department of Psychology, University of Toronto, Toronto, ON, Canada.

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, meanage = 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.

KEYWORDS:

GST; Intellectual functioning; Medulloblastoma; PPAR; Random forest

PMID:
30607709
DOI:
10.1007/s11060-018-03083-x

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