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

Publication ,  Journal Article
Zhang, C; Ostrom, QT; Semmes, EC; Ramaswamy, V; Hansen, HM; Morimoto, L; de Smith, AJ; Pekmezci, M; Vaksman, Z; Hakonarson, H; Diskin, SJ ...
Published in: Acta Neuropathol Commun
October 28, 2020

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.

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Published In

Acta Neuropathol Commun

DOI

EISSN

2051-5960

Publication Date

October 28, 2020

Volume

8

Issue

1

Start / End Page

173

Location

England

Related Subject Headings

  • Young Adult
  • Telomere-Binding Proteins
  • Telomere Homeostasis
  • Telomere
  • Telomerase
  • Ribonucleoproteins
  • RNA
  • Mendelian Randomization Analysis
  • Male
  • Infratentorial Neoplasms
 

Citation

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Zhang, C., Ostrom, Q. T., Semmes, E. C., Ramaswamy, V., Hansen, H. M., Morimoto, L., … Walsh, K. M. (2020). Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma. Acta Neuropathol Commun, 8(1), 173. https://doi.org/10.1186/s40478-020-01038-w
Zhang, Chenan, Quinn T. Ostrom, Eleanor C. Semmes, Vijay Ramaswamy, Helen M. Hansen, Libby Morimoto, Adam J. de Smith, et al. “Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma.Acta Neuropathol Commun 8, no. 1 (October 28, 2020): 173. https://doi.org/10.1186/s40478-020-01038-w.
Zhang C, Ostrom QT, Semmes EC, Ramaswamy V, Hansen HM, Morimoto L, et al. Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma. Acta Neuropathol Commun. 2020 Oct 28;8(1):173.
Zhang, Chenan, et al. “Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma.Acta Neuropathol Commun, vol. 8, no. 1, Oct. 2020, p. 173. Pubmed, doi:10.1186/s40478-020-01038-w.
Zhang C, Ostrom QT, Semmes EC, Ramaswamy V, Hansen HM, Morimoto L, de Smith AJ, Pekmezci M, Vaksman Z, Hakonarson H, Diskin SJ, Metayer C, Glioma International Case-Control Study (GICC), Taylor MD, Wiemels JL, Bondy ML, Walsh KM. Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma. Acta Neuropathol Commun. 2020 Oct 28;8(1):173.
Journal cover image

Published In

Acta Neuropathol Commun

DOI

EISSN

2051-5960

Publication Date

October 28, 2020

Volume

8

Issue

1

Start / End Page

173

Location

England

Related Subject Headings

  • Young Adult
  • Telomere-Binding Proteins
  • Telomere Homeostasis
  • Telomere
  • Telomerase
  • Ribonucleoproteins
  • RNA
  • Mendelian Randomization Analysis
  • Male
  • Infratentorial Neoplasms