Investigation of established genetic risk variants for glioma in pre-diagnostic samples from a population based nested case control study
Couplée à une étude en population norvégienne incluant 598 cas et 595 témoins et menée sur des échantillons sériques, cette étude prospective évalue l'association entre 11 variants génétiques précédemment identifiés dans trois études d'association sur le génome entier et le risque de gliome
Background: Although glioma aetiology is poorly understood in general, growing evidence indicates a genetic component. Three large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case-control design, where cases have been recruited at the time of, or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included. Methods: To confirm glioma risk variants in a prospective setting, we have analysed 11 previously identified risk variants in a set of pre-diagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population based biobank reserved for cancer research. Results: We confirmed the association with glioma risk for variants within five genomic regions; 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study. Conclusions: Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk, and may consequently impact gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants, or markers for glioma prognosis. Impact: Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus aetiology.