Genetic risk profiles identify different molecular etiologies for glioma.
OBJECTIVE
Genome-wide association studies have recently identified single-nucleotide polymorphisms (SNP) in five loci at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756, CDKN2A/CDKN2B), 20q13.33 (rs6010620, RTEL1), and 11q23.3 (rs498872, PHLDB1) to be associated with glioma risk. Because gliomas are heterogeneous in histology, molecular alterations, and clinical behavior, we have investigated these polymorphisms for potential correlations with tumor histology and patient survival.


METHODS
We studied the relationship between SNPs and glioma subtype in two large patient cohorts from France and Germany, totaling 1,577 patients, as well as the relationship between SNP genotype and overall survival.


RESULTS
In both cohorts, the frequencies of rs2736100 and rs6010620 risk genotypes were highly correlated with high-grade disease (P < 0.001), whereas rs4295627 and rs498872 risk genotypes were inversely related to tumor grade (P < 0.001). These data show that genetic variations at these loci have subtype-specific effects on the risk of developing glioma. In contrast, the rs4977756 genotype was not correlated with tumor grade, consistent with the causal variant having a generic influence on glioma development. None of the five SNPs was associated with prognosis independent of tumor grade.


CONCLUSIONS
Our findings provide novel insight into etiologic pathways in the different glioma subtypes.
Simon
Matthias
M
Neurochirurgische Klinik, Universitätskliniken Bonn, Bonn, Germany. Matthias.Simon@ukb.uni-bonn.de
Hosking
Fay J
FJ
Marie
Yannick
Y
Gousias
Konstantinos
K
Boisselier
Blandine
B
Carpentier
Catherine
C
Schramm
Johannes
J
Mokhtari
Karima
K
Hoang-Xuan
Khe
K
Idbaih
Ahmed
A
Delattre
Jean-Yves
JY
Lathrop
Mark
M
Robertson
Lindsay B
LB
Houlston
Richard S
RS
Sanson
Marc
M
D000328:Adult; D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005910:Glioma / Q000145:classification* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D016019:Survival Analysis; D055815:Young Adult