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- Title
Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma.
- Authors
Zhang, Chenan; Ostrom, Quinn T.; Semmes, Eleanor C.; Ramaswamy, Vijay; Hansen, Helen M.; Morimoto, Libby; de Smith, Adam J.; Pekmezci, Melike; Vaksman, Zalman; Hakonarson, Hakon; Diskin, Sharon J.; Metayer, Catherine; The Glioma International Case-Control Study (GICC); Claus, Elizabeth B.; Il'yasova, Dora; Walsh, Kyle M.; Schildkraut, Joellen; Barnholtz-Sloan, Jill S.; Olson, Sara H.; Bernstein, Jonine L.
- 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.
- Subjects
CALIFORNIA; TORONTO (Ont.); TELOMERES; CHILDREN'S Hospital of Philadelphia; TUMORS in children; CHILDREN'S hospitals; BRAIN tumors; EPENDYMOMA
- Publication
Acta Neuropathologica Communications, 2020, Vol 8, Issue 1, pN.PAG
- ISSN
2051-5960
- Publication type
Article
- DOI
10.1186/s40478-020-01038-w