title: Chromosome 7p11.2 (EGFR) variation influences 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, 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.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l’Institut du Cerveau et de la Moëlle épinière/UMR-S975, GH Pitié-Salpêtrière, 47 boulevard de l'Hôpital, Paris, France.
authors.forename: Marc
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authors.lastname: Sanson
authors.forename: Fay J
authors.initials: FJ
authors.lastname: Hosking
authors.forename: Sanjay
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authors.lastname: Shete
authors.forename: Diana
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authors.lastname: Zelenika
authors.forename: Sara E
authors.initials: SE
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authors.forename: Yussanne
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authors.lastname: Ma
authors.forename: Victor
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authors.lastname: Enciso-Mora
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authors.forename: Yannick
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authors.lastname: Marie
authors.forename: Blandine
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authors.lastname: Carpentier
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authors.lastname: Wang
authors.forename: Anna Luisa
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authors.lastname: Di Stefano
authors.forename: Marianne
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authors.lastname: Labussière
authors.forename: Konstantinos
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authors.lastname: Gousias
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authors.lastname: Schramm
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authors.lastname: Boland
authors.forename: Doris
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authors.lastname: Lechner
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authors.lastname: Gut
authors.forename: Georgina
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authors.lastname: Armstrong
authors.forename: Yanhong
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authors.lastname: Liu
authors.forename: Robert
authors.initials: R
authors.lastname: Yu
authors.forename: Ching
authors.initials: C
authors.lastname: Lau
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Di Bernardo
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Robertson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Muir
authors.forename: Sarah
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authors.lastname: Hepworth
authors.forename: Anthony
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authors.lastname: Swerdlow
authors.forename: Minouk J
authors.initials: MJ
authors.lastname: Schoemaker
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Martina
authors.initials: M
authors.lastname: Müller
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.forename: Lewin
authors.initials: L
authors.lastname: Eisele
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Melissa
authors.initials: M
authors.lastname: Bondy
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Matthias
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authors.lastname: Simon
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D055106:Genome-Wide Association Study; D005910:Glioma / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors