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

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Sanson, M., Hosking, Fay J., Shete, Sanjay, Zelenika, D., Dobbins, Sara E., Ma, Yussanne, Enciso-Mora, V., Idbaih, A., Delattre, Jean-Yves, Hoang-Xuan, K. et al.
(2011) Chromosome 7p11.2 (EGFR) variation influences glioma risk. Human Molecular Genetics, Vol.20 (No.14). pp. 2897-2904. doi:10.1093/hmg/ddr192 ISSN 0964-6906.

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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 x 10(-8) and 2.09 x 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.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Epidermal growth factor -- Receptors, Gliomas -- Risk factors -- Research
Journal or Publication Title: Human Molecular Genetics
Publisher: Oxford University Press
ISSN: 0964-6906
Official Date: 15 July 2011
Dates:
DateEvent
15 July 2011Published
Volume: Vol.20
Number: No.14
Page Range: pp. 2897-2904
DOI: 10.1093/hmg/ddr192
Status: Peer Reviewed
Publication Status: Published
Funder: Cancer Research UK (CRUK), DJ Fielding Medical Research Trust, European Union (EU), International Union against Cancer (UICC) , Mobile Manufacturers' Forum and Global System for Mobile Communications Association (GSMA), Mobile Telecommunications and Health Research Programme (Great Britain) (MTHR), Great Britain. Dept. of Health (DoE), UK Network Operators' Forum (UKNOF), National Institutes of Health (U.S.) (NIH), American Brain Tumor Association (ABTA), National Brain Tumor Society (U.S.) (NBTS) , Délégation à la Recherche Clinique et à l'Innovation (DRCI) , Association pour la Recherche sur les Tumeurs Cerebrales (ARTC) , Institut National du Cancer (France) (INCa) , France. Ministère de l'enseignement supérieur et de la recherche (MESR), Deutsche Forschungsgemeinschaft (DFG) , Deutsche Krebshilfe , Universität Bonn. Medizinische Fakultät (BONFOR), Wellcome Trust (London, England), Germany. Bundesministerium für Bildung und Forschung (BMBF) , Helmholtz Zentrum München [German Research Center for Environmental Health], German National Genome Research Network (NGFN) within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ
Grant number: C1298/A8362 (WT & CRUK), QLK4-CT-1999-0C1563 (EU), 5R01(A1192155R01, CA070917) (NIH), MUL03012 (DRCI), PL046 (INCa), Si552 Schr285 (DFG), 70-2385-Wi2 (DK), 70-3163-Wi3 (DK), 10-6262 (DK), 076113 (WT), 085475 (WT)

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