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

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

Marc Sanson  1 , 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
Affiliations
Comparative Study

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

Marc Sanson et al. Hum Mol Genet. .

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.

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Figures

Figure 1.
Figure 1.
Plot of association results and recombination rates for the 7p11.2 (EGFR) region. –log10P-values (y-axis) of the SNPs are shown according to their chromosomal positions (x-axis). The top two genotyped SNPs, rs11979158 and rs2252586, are labeled. The color intensity of each symbol reflects the extent of LD with the top genotyped SNP; r2 > 0.8 being represented with blue (with rs11979158) and red (with rs2252586) through to white (r2 < 0.2). Genetic recombination rates (cM/Mb), estimated using HapMap CEU samples, are shown with a light blue line. Physical positions are based on build 36 (NCBI) of the human genome. Also shown is the relative position of EGFR.
Figure 2.
Figure 2.
Cumulative effect of glioma risk alleles. Plot of increasing ORs for glioma for increasing number of risk alleles. The ORs are relative to the median number of eight risk alleles; vertical bars correspond to 95% CIs. Horizontal line marks the null value (OR = 1.0).
Figure 3.
Figure 3.
Relationship between 7p11.2 genotype and WHO tumor grade. Also shown are the relationships between histology and 5p15.33 (rs2736100), 8q24.21 (rs4295627), 9p21.3 (rs4977756), 20q13.33 (rs6010620) and 11q23.3 (rs498872) genotypes. *Significant association at P< 0.05.
Figure 4.
Figure 4.
Patient exclusion schema for the genome-wide studies.
See this image and copyright information in PMC

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