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Jeanette E Eckel-Passow1, Paul A Decker1, Matt L Kosel1

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Genetic risk scores using 25 single nucleotide polymorphisms (SNPs) can help identify individuals at higher risk for developing isocitrate dehydrogenase (IDH) mutant glioma. These scores may aid in managing brain lesions in specific high-risk patient groups.

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Area of Science:

  • Neuro-oncology
  • Genetics
  • Epidemiology

Background:

  • Twenty-five single nucleotide polymorphisms (SNPs) are linked to adult diffuse glioma risk.
  • A hypothesis was formed that these SNPs, along with age and sex, could predict glioma risk and subtypes.

Purpose of the Study:

  • To develop and validate models for estimating glioma risk and identifying subtypes.
  • To predict isocitrate dehydrogenase (IDH) mutation status using genetic markers.

Main Methods:

  • Case-control and case-case designs with logistic regression were employed.
  • Multinomial logistic regression was used for risk and subtype estimation.
  • Discovery (1273 cases, 443 controls) and validation (852 cases, 231 controls) sets were utilized, with genotyping via Illumina OncoArray.

Main Results:

  • The highest risk score group (top 5%) showed over a 14-fold increased relative risk for IDH mutant glioma.
  • Lifetime risk for IDH mutant gliomas ranged from near zero to 2.3% (non-codeleted) and 1.7% (codeleted).
  • The SNP-based model for IDH mutation prediction achieved a validation concordance index of 0.85.

Conclusions:

  • Germline genotyping offers potential tools for managing newly discovered brain lesions.
  • Risk scores are not suitable for general population screening due to low glioma incidence.
  • These scores may prove valuable for risk stratification in specific, defined high-risk populations.