Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma.

ABSTRACT: 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.

SUBMITTER: Zhang C 

PROVIDER: S-EPMC7592366 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature