Chromosome 7p11.2 (EGFR) variation influences glioma risk

TLDR

Gliomas are the most common primary brain tumors, yet their etiology remains largely unknown. The study aimed to identify novel glioma risk loci through genome‑wide association analysis of French and German case–control series. The analysis combined these data with UK and US GWAS, yielding 4147 glioma cases and 7435 controls genotyped across 424,460 common SNPs. The combined GWAS revealed two independent associations at 7p11.2 (rs11979158 and rs2252586) near EGFR, independent of tumor subtype, EGFR amplification, p16INK4a deletion, and IDH1 mutation, indicating that 7p11.2 variation is a determinant of inherited glioma risk.

Abstract

While gliomas are the most common primary brain tumors, their etiology is largely unknown. To identify novel risk loci for glioma, we conducted genome-wide association (GWA) analysis of two case–control series from France and Germany (2269 cases and 2500 controls). Pooling these data with previously reported UK and US GWA studies provided data on 4147 glioma cases and 7435 controls genotyped for 424 460 common tagging single-nucleotide polymorphisms. Using these data, we demonstrate two statistically independent associations between glioma and rs11979158 and rs2252586, at 7p11.2 which encompasses the EGFR gene (population-corrected statistics, Pc = 7.72 × 10−8 and 2.09 × 10−8, respectively). Both associations were independent of tumor subtype, and were independent of EGFR amplification, p16INK4a deletion and IDH1 mutation status in tumors; compatible with driver effects of the variants on glioma development. These findings show that variation in 7p11.2 is a determinant of inherited glioma risk.