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

Hum Mol Genet. 2011 Jul 15;20(14):2897-904. doi: 10.1093/hmg/ddr192. Epub 2011 Apr 29.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Chromosomes, Human, Pair 7 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • ErbB Receptors / genetics*
  • Female
  • Gene Amplification*
  • Gene Deletion
  • Genome-Wide Association Study
  • Glioma / epidemiology
  • Glioma / genetics*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Male
  • Polymorphism, Single Nucleotide*
  • Risk Factors

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • EGFR protein, human
  • ErbB Receptors