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

Authors:
Marc Sanson, Fay J Hosking, Sanjay Shete, Diana Zelenika, Sara E Dobbins, Yussanne Ma, Victor Enciso-Mora, Ahmed Idbaih, Jean-Yves Delattre, Khe Hoang-Xuan, Yannick Marie, Blandine Boisselier, Catherine Carpentier, Xiao-Wei Wang, Anna Luisa Di Stefano, Marianne Labussière, Konstantinos Gousias, Johannes Schramm, Anne Boland, Doris Lechner, Ivo Gut, Georgina Armstrong, Yanhong Liu, Robert Yu, Ching Lau, Maria Chiara Di Bernardo, Lindsay B Robertson, Kenneth Muir, Sarah Hepworth, Anthony Swerdlow, Minouk J Schoemaker, H-Erich Wichmann, Martina Müller, Stefan Schreiber, Andre Franke, Susanne Moebus, Lewin Eisele, Asta Försti, Kari Hemminki, Mark Lathrop, Melissa Bondy, Richard S Houlston, Matthias Simon
Year of publication:
2011
Volume:
20
Issue:
14
Issn:
0964-6906
Journal title abbreviated:
HUM MOL GENET
Journal title long:
Human molecular genetics
Impact factor:
5.985
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, P(c) = 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.