Identification of glutathione S-transferase (GST) polymorphisms in brain tumors and association with susceptibility to pediatric astrocytomas

Rona Ezer, Michelle Alonso, Elaine Pereira, Mimi Kim, Jeffrey C. Allen, Douglas C. Miller, Elizabeth W. Newcomb

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Polymorphisms in the glutathione S-transferase (GST) genes, a superfamily that plays a key role in carcinogen metabolism, have been associated with an increased susceptibility to several types of cancer. We wished to evaluate whether variant allelic forms of GST isoenzymes were associated with an increased susceptibility for brain tumors and age of tumor onset. Here, we examined 394 brain tumors (221 adult and 173 pediatric cases consisting of 197 astrocytic and 197 non-astrocytic tumors) to determine the frequency of polymorphisms in the GSTM1, GSTT1, and GSTP1 genes compared to a healthy control population. Our data shows that the frequency of GST polymorphisms varies not only between adult and pediatric patients with brain tumors and healthy controls, but also between different histological subtypes of brain tumors occurring in pediatric patients. We found (i) a statistically significant increase in the frequency of the functional GSTM1 allele in high-grade pediatric astrocytomas (p < 0.002), (ii) a significant increase in the frequency of the rare GSTP1 variant Val114/Val114 in pediatric astrocytomas (p < 0.002), and (iii) a significant increase in the frequency of the rare GSTP1 Val114/Val114 genotype among pediatric tumors showing microsatellite instability (MSI) due to defects in mismatch repair (MMR) proteins (p = 0.003). Our results suggest that GSTM1 and GSTP1 polymorphisms may play a role in brain tumor susceptibility by histological subtype, particularly high-grade pediatric astrocytomas. Moreover, the presence of the genetic modifier GSTP1 Val114/Val114 genotype may begin to define a high-risk genotype for cancer susceptibility in the pediatric population.

Original languageEnglish (US)
Pages (from-to)123-134
Number of pages12
JournalJournal of Neuro-Oncology
Volume59
Issue number2
DOIs
StatePublished - Sep 2002
Externally publishedYes

Fingerprint

Astrocytoma
Glutathione Transferase
Brain Neoplasms
Pediatrics
Genotype
Neoplasms
Microsatellite Instability
DNA Mismatch Repair
Age of Onset
Carcinogens
Population
Isoenzymes
Genes
Alleles

Keywords

  • Genetic susceptibility
  • Glutathione S-transferase
  • Microsatellite instability
  • Pediatric astrocytomas
  • Polymorphisms

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

Identification of glutathione S-transferase (GST) polymorphisms in brain tumors and association with susceptibility to pediatric astrocytomas. / Ezer, Rona; Alonso, Michelle; Pereira, Elaine; Kim, Mimi; Allen, Jeffrey C.; Miller, Douglas C.; Newcomb, Elizabeth W.

In: Journal of Neuro-Oncology, Vol. 59, No. 2, 09.2002, p. 123-134.

Research output: Contribution to journalArticle

Ezer, Rona ; Alonso, Michelle ; Pereira, Elaine ; Kim, Mimi ; Allen, Jeffrey C. ; Miller, Douglas C. ; Newcomb, Elizabeth W. / Identification of glutathione S-transferase (GST) polymorphisms in brain tumors and association with susceptibility to pediatric astrocytomas. In: Journal of Neuro-Oncology. 2002 ; Vol. 59, No. 2. pp. 123-134.
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