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

Autor: Chenan Zhang, Quinn T. Ostrom, Eleanor C. Semmes, Vijay Ramaswamy, Helen M. Hansen, Libby Morimoto, Adam J. de Smith, Melike Pekmezci, Zalman Vaksman, Hakon Hakonarson, Sharon J. Diskin, Catherine Metayer, The Glioma International Case-Control Study (GICC), Michael D. Taylor, Joseph L. Wiemels, Melissa L. Bondy, Kyle M. Walsh
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-12 (2020)
Druh dokumentu: article
ISSN: 2051-5960
98851748
DOI: 10.1186/s40478-020-01038-w
Popis: 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.
Databáze: Directory of Open Access Journals
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