Different Aetiology of Familial Low-grade and High-grade Glioma? A Nationwide Cohort Study of Familial Glioma

An increased risk for first-degree relatives (FDR) of glioma patients has previously been observed. The novel objective of this study was to investigate differences in familial risk among FDR of low-grade glioma (LGG) and high-grade glioma (HGG) cases, respectively. Two cohorts were constructed, one from 15,321 FDR of LGG cases and the other from 26,635 FDR of HGG cases calculating standardised incidence ratios (SIR). The risk for LGG among FDR of LGG cases was significantly increased, SIR 3.65 (95% CI 2.31-5.47). The risk was even higher in the cohort of siblings, SIR 7.00 (95% CI 3.35-12.87), and especially in the younger siblings (<40 years), SIR 9.01 (95% CI 4.31-16.57). When calculating the risk for HGG in the LGG cohort and the risk for HGG in the HGG cohort, there was a generally twofold increased risk, but no trends of increased risk in relatives of younger probands. Two different methods calculating familial risk displayed similar results. LGG families apparently have features manifesting a distinct pedigree pattern with sibpairs affected at a young age. These families could provide new insights into the aetiology of glioma.