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

Details

• Alternative Title:
  Int J Cancer
• Personal Author:
  Ostrom, Quinn T. ; Kinnersley, Ben ; Armstrong, Georgina ; Rice, Terri ; Chen, Yanwen ; Wiencke, John K. ; McCoy, Lucie S. ; Hansen, Helen M. ; Amos, Christopher I. ; Bernstein, Jonine L. ; Claus, Elizabeth B. ; Eckel-Passow, Jeanette E. ; Il’yasova, Dora ; Johansen, Christoffer ; Lachance, Daniel H. ; Lai, Rose K. ; Merrell, Ryan T. ; Olson, Sara H. ; Sadetzki, Siegal ; Schildkraut, Joellen M. ; Shete, Sanjay ; Rubin, Joshua B. ; Andersson, Ulrika ; Rajaraman, Preetha ; Chanock, Stephen J. ; Linet, Martha S. ; Wang, Zhaoming ; Yeager, Meredith ; Houlston, Richard S. ; Jenkins, Robert B. ; Wrensch, Margaret R. ; Melin, Beatrice ; Bondy, Melissa L. ; Barnholtz-Sloan, Jill. S.
• Description:
  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 [p| = 1.50x10| , OR| = 1.28, 95%CI| = 1.18-1.39; p| = 2.14x10| , OR| = 1.32, 95%CI| = 1.21-1.43] and rs11979158 [p| = 6.13x10| , OR| = 1.35, 95%CI| = 1.21-1.50; p| = 2.18x10| , OR| = 1.42, 95%CI| = 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 (p| = 9.30 × 10| , OR| = 1.76, 95%CI| = 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.'
• Subjects:
  Adolescent Adult Aged Age Factors Brain Neoplasms Case-Control Studies Female Genome-Wide Association Study Glioblastoma Humans Male Middle Aged Neoplasm Grading Polymorphism, Single Nucleotide Young Adult

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• Source:
  Int J Cancer. 143(10):2359-2366
• Pubmed ID:
  30152087
• Pubmed Central ID:
  PMC6205887
• Document Type:
  Journal Article
• Funding:
  HHSN261201000140C/CA/NCI NIH HHSUnited States/ ; U58DP003862-01/CC/CDC HHSUnited States/ ; HHSN261201000035C/CA/NCI NIH HHSUnited States/ ; P50CA097257/NH/NIH HHSUnited States/ ; UM1 CA182934/CA/NCI NIH HHSUnited States/ ; R01 CA126831/CA/NCI NIH HHSUnited States/ ; UL1 RR024131/RR/NCRR NIH HHSUnited States/ ; 30CA125123P50097257R01CA126831R01CA139020R01CA52689/CA/NCI NIH HHSUnited States/ ; P30 CA125123/CA/NCI NIH HHSUnited States/ ; P50 CA097257/CA/NCI NIH HHSUnited States/ ; R01 CA207360/CA/NCI NIH HHSUnited States/ ; R01CA52689/NH/NIH HHSUnited States/ ; TR/NCATS NIH HHSUnited States/ ; R01 CA139020/CA/NCI NIH HHSUnited States/ ; HHSN261201000140CP/CA/NCI NIH HHSUnited States/ ; P30 CA008748/CA/NCI NIH HHSUnited States/ ; P30CA125123/NH/NIH HHSUnited States/ ; P50097257/NH/NIH HHSUnited States/ ; UK10K/WT_/Wellcome TrustUnited Kingdom/ ; R01CA126831/NH/NIH HHSUnited States/ ; R01CA139020/NH/NIH HHSUnited States/ ; HHSN261201000034C/CA/NCI NIH HHSUnited States/ ; U58 DP003862/DP/NCCDPHP CDC HHSUnited States/ ; WT_/Wellcome TrustUnited Kingdom/ ; R01 CA052689/CA/NCI NIH HHSUnited States/ ; CC/CDC HHSUnited States/
• Volume:
  143
• Issue:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:13fa9dcbf8f508fc72f4f89443539f372990377aed456882d91cd3e059ec671b
• Download URL:
  https://stacks.cdc.gov/view/cdc/60142/cdc_60142_DS1.pdf
• File Type:
  [PDF - 717.18 KB ]