Department of Medicine, Section of Epidemiology and Population Sciences, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Int J Cancer. 2018 Nov 15;143(10):2359-2366. doi: 10.1002/ijc.31759. Epub 2018 Sep 19.
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.'
胶质母细胞瘤（GBM）是美国最常见的恶性脑肿瘤。GBM 的发病率随年龄增长而增加，诊断时年龄较小与预后改善显著相关。虽然候选 GBM 风险单核苷酸多态性（SNP）与发病年龄的关系已被探索，但全基因组关联研究（GWAS）以前并未按年龄分层。使用来自四项先前 GWAS 的数据，在常染色体 SNP 中评估了潜在的年龄特异性遗传效应。使用年龄分布三分位（18-53、54-64、65+）数据集，使用年龄分层逻辑回归进行分析，生成 p 值、比值比（OR）和 95%置信区间（95%CI），然后使用荟萃分析进行合并。共有 4512 例 GBM 病例和 10582 例对照用于分析。在 7p11.2 中检测到两个先前确定的 SNP 存在显著关联(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]和 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])，但仅在年龄>54 的人群中存在。在先前确定的低级别胶质瘤（LGG）风险位点 8q24.21(rs55705857)也存在显著关联，在 18-53 岁人群中（p=9.30x10,OR=1.76,95%CI=1.49-2.10）。在癌症基因组图谱（TCGA）中，在 18-53 岁的 GBM 样本中，存在更多的“LGG”样肿瘤特征，IDH1/2 突变频率为 15%，而 54-63 岁为 2.1%[54-63]和 64+为 0.8%[64+]（p=0.0005）。癌症易感性的年龄特异性差异可为病因学提供重要线索。在年龄<54 岁的个体中，已知与 IDH1/2 突变型胶质瘤相关的 SNP 以及 IDH1/2 突变的更高发生率的关联表明，更多的年轻个体可能最初表现为“继发性胶质母细胞瘤”。
