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. 2018 Nov 15;143(10):2359-2366.
doi: 10.1002/ijc.31759. Epub 2018 Sep 19.

Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age

Quinn T Ostrom  1   2   3 , Ben Kinnersley  4 , Georgina Armstrong  1 , Terri Rice  5 , Yanwen Chen  2 , John K Wiencke  5 , Lucie S McCoy  5 , Helen M Hansen  5 , Christopher I Amos  6 , Jonine L Bernstein  7 , Elizabeth B Claus  8   9 , Jeanette E Eckel-Passow  10 , Dora Il'yasova  11   12   13 , Christoffer Johansen  14 , Daniel H Lachance  15 , Rose K Lai  16 , Ryan T Merrell  17 , Sara H Olson  7 , Siegal Sadetzki  18   19 , Joellen M Schildkraut  20 , Sanjay Shete  21 , Joshua B Rubin  22 , Ulrika Andersson  23 , Preetha Rajaraman  24 , Stephen J Chanock  24   25 , Martha S Linet  24 , Zhaoming Wang  24   25   26 , Meredith Yeager  24   25 ; GliomaScan consortium; Richard S Houlston  4 , Robert B Jenkins  27 , Margaret R Wrensch  5 , Beatrice Melin  23 , Melissa L Bondy  1 , Jill S Barnholtz-Sloan  2
Affiliations

Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age

Quinn T Ostrom et al. Int J Cancer. .

Abstract

Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18-53, 54-64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54-63 = 1.50x10-9 , OR54-63 = 1.28, 95%CI54-63 = 1.18-1.39; p64+ = 2.14x10-11 , OR64+ = 1.32, 95%CI64+ = 1.21-1.43] and rs11979158 [p54-63 = 6.13x10-8 , OR54-63 = 1.35, 95%CI54-63 = 1.21-1.50; p64+ = 2.18x10-10 , OR64+ = 1.42, 95%CI64+ = 1.27-1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18-53 (p18-53 = 9.30 × 10-11 , OR18-53 = 1.76, 95%CI18-53 = 1.49-2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of 'LGG'-like tumor characteristics in GBM samples in those 18-53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54-63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18-53 suggests that more younger individuals may present initially with 'secondary glioblastoma.'

Keywords: age; brain tumors; glioma.

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Conflict of interest statement

Conflict of Interest: There are no conflicts of interest to report.

Figures

Figure 1.
Figure 1.
Study schematic for a) age-stratified case-control analyses, and b) case-only analyses
Figure 2.
Figure 2.
Case only estimates for SNPs identified as being significantly associated with age-at-diagnosis in this or prior analyses in a) all ages, b) cases ages 54+
See this image and copyright information in PMC

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