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Age-specific genome-wide association study in glioblastoma identifies increased proportion of ‘lower grade glioma’-like features associated with younger age
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September 19 2018
Source: Int J Cancer. 143(10):2359-2366
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Alternative Title:Int J Cancer
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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.'
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Pubmed ID:30152087
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Pubmed Central ID:PMC6205887
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