| Literature DB >> 30152087 |
Quinn T Ostrom1,2,3, Ben Kinnersley4, Georgina Armstrong1, Terri Rice5, Yanwen Chen2, John K Wiencke5, Lucie S McCoy5, Helen M Hansen5, Christopher I Amos6, Jonine L Bernstein7, Elizabeth B Claus8,9, Jeanette E Eckel-Passow10, Dora Il'yasova11,12,13, Christoffer Johansen14, Daniel H Lachance15, Rose K Lai16, Ryan T Merrell17, Sara H Olson7, Siegal Sadetzki18,19, Joellen M Schildkraut20, Sanjay Shete21, Joshua B Rubin22, Ulrika Andersson23, Preetha Rajaraman24, Stephen J Chanock24,25, Martha S Linet24, Zhaoming Wang24,25,26, Meredith Yeager24,25, Richard S Houlston4, Robert B Jenkins27, Margaret R Wrensch5, Beatrice Melin23, Melissa L Bondy1, Jill S Barnholtz-Sloan2.
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.'Entities:
Keywords: age; brain tumors; glioma
Mesh：
Year: 2018 PMID： 30152087 PMCID： PMC6205887 DOI： 10.1002/ijc.31759
Source DB: PubMed Journal: Int J Cancer ISSN： 0020-7136 Impact factor: 7.316