Is intracranial volume a risk factor for IDH-mutant low-grade glioma? A case-control study

J Neurooncol. 2022 Oct;160(1):101-106. doi: 10.1007/s11060-022-04120-6. Epub 2022 Aug 27.


Purpose: Risk of cancer has been associated with body or organ size in several studies. We sought to investigate the relationship between intracranial volume (ICV) (as a proxy for lifetime maximum brain size) and risk of IDH-mutant low-grade glioma.

Methods: In a multicenter case-control study based on population-based data, we included 154 patients with IDH-mutant WHO grade 2 glioma and 995 healthy controls. ICV in both groups was calculated from 3D MRI brain scans using an automated reverse brain mask method, and then compared using a binomial logistic regression model.

Results: We found a non-linear association between ICV and risk of glioma with increasing risk above and below a threshold of 1394 ml (p < 0.001). After adjusting for ICV, sex was not a risk factor for glioma.

Conclusion: Intracranial volume may be a risk factor for IDH-mutant low-grade glioma, but the relationship seems to be non-linear with increased risk both above and below a threshold in intracranial volume.

Keywords: Brain neoplasms; HUNT study; Low-grade glioma; Magnetic resonance imaging; Risk factors.

Publication types

  • Multicenter Study

MeSH terms

  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / genetics
  • Case-Control Studies
  • Glioma* / diagnostic imaging
  • Glioma* / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Magnetic Resonance Imaging / methods
  • Mutation
  • Risk Factors


  • Isocitrate Dehydrogenase