Ependymoma is the third most common brain tumor in children, with well-described molecular characterization but poorly understood underlying germline risk factors. To investigate whether genetic predisposition to longer telomere length influences ependymoma risk, we utilized case–control data from three studies: a population-based pediatric and adolescent ependymoma case–control sample from California (153 cases, 696 controls), a hospital-based pediatric posterior fossa type A (EPN-PF-A) ependymoma case–control study from Toronto’s Hospital for Sick Children and the Children’s Hospital of Philadelphia (83 cases, 332 controls), and a multicenter adult-onset ependymoma case–control dataset nested within the Glioma International Case-Control Consortium (GICC) (103 cases, 3287 controls). In the California case–control sample, a polygenic score for longer telomere length was significantly associated with increased risk of ependymoma diagnosed at ages 12–19 (P = 4.0 × 10−3), but not with ependymoma in children under 12 years of age (P = 0.94). Mendelian randomization supported this observation, identifying a significant association between genetic predisposition to longer telomere length and increased risk of adolescent-onset ependymoma (ORPRS = 1.67; 95% CI 1.18–2.37; P = 3.97 × 10−3) and adult-onset ependymoma (PMR-Egger = 0.042), but not with risk of ependymoma diagnosed before age 12 (OR = 1.12; 95% CI 0.94–1.34; P = 0.21), nor with EPN-PF-A (PMR-Egger = 0.59). These findings complement emerging literature suggesting that augmented telomere maintenance is important in ependymoma pathogenesis and progression, and that longer telomere length is a risk factor for diverse nervous system malignancies.

中文翻译：

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端粒长度较长的遗传倾向以及儿童、青少年和成人发病室管膜瘤的风险


室管膜瘤是儿童中第三大常见的脑肿瘤，其分子特征已得到充分描述，但对潜在的种系危险因素知之甚少。为了调查端粒长度较长的遗传倾向是否会影响室管膜瘤风险，我们利用了三项研究的病例对照数据：来自加利福尼亚州的一项基于人群的儿科和青少年室管膜瘤病例对照样本（153 例病例，696 名对照）、一项基于医院的儿科研究多伦多病童医院和费城儿童医院的后颅窝 A 型 (EPN-PF-A) 室管膜瘤病例对照研究（83 例，332 名对照），以及嵌套在胶质瘤国际病例对照联盟 (GICC)（103 例病例，3287 例对照）。在加州病例对照样本中，较长端粒长度的多基因评分与 12-19 岁诊断出的室管膜瘤风险增加显着相关 (P = 4.0 × 10−3)，但与 12 岁以下儿童的室管膜瘤风险无关（P = 0.94）。孟德尔随机化支持了这一观察结果，确定端粒长度较长的遗传倾向与青少年发病室管膜瘤风险增加（ORPRS = 1.67；95% CI 1.18–2.37；P = 3.97 × 10−3）和成人发病室管膜瘤风险增加之间存在显着关联。 (PMR-Egger = 0.042)，但与 12 岁之前诊断出的室管膜瘤风险无关 (OR = 1.12；95% CI 0.94–1.34；P = 0.21)，也与 EPN-PF-A (PMR-Egger = 0.59) 无关。这些发现补充了新出现的文献，表明增强端粒维持在室管膜瘤发病机制和进展中很重要，并且较长的端粒长度是多种神经系统恶性肿瘤的危险因素。