Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of glioma.
Much of the variation in inherited risk of glioma is likely to be explained by combinations of common low risk variants. The established relationship between glioma risk and exposure to ionizing radiation led us to examine whether variants in the DNA repair genes contribute to disease susceptibility. We evaluated 1127 haplotype-tagging single-nucleotide polymorphisms (SNPs) supplemented with 388 putative functional SNPs to capture most of the common variation in 136 DNA repair genes, in five unique case-control series from four different countries (1013 cases, 1016 controls). We identified 16 SNPs associated with glioma risk at the 1% significance level. The highest association observed across the five independent case-control datasets involved rs243356, which maps to intron 3 of CHAF1A (trend odds ratio, 1.32; 95% confidence interval 1.14-1.54; P = 0.0002; false-positive report probability = 0.055, based on a prior probability of 0.01). Our results provide additional support for the hypothesis that low penetrance variants contribute to the risk of developing glioma and suggest that a genetic variant located in or around the CHAF1A gene contributes to disease risk.
Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey SM2 5NG, UK.
Lara
L
Bethke
Emily
E
Webb
Anne
A
Murray
Minouk
M
Schoemaker
Christoffer
C
Johansen
Helle Collatz
HC
Christensen
Kenneth
K
Muir
Patricia
P
McKinney
Sarah
S
Hepworth
Polyxeni
P
Dimitropoulou
Artitaya
A
Lophatananon
Maria
M
Feychting
Stefan
S
Lönn
Anders
A
Ahlbom
Beatrice
B
Malmer
Roger
R
Henriksson
Anssi
A
Auvinen
Anne
A
Kiuru
Tiina
T
Salminen
Anthony
A
Swerdlow
Richard
R
Houlston
D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005910:Glioma / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide