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

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.