TY - JOUR
T1 - Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma
AU - The Glioma International Case-Control Study (GICC)
AU - Zhang, Chenan
AU - Ostrom, Quinn T.
AU - Semmes, Eleanor C.
AU - Ramaswamy, Vijay
AU - Hansen, Helen M.
AU - Morimoto, Libby
AU - de Smith, Adam J.
AU - Pekmezci, Melike
AU - Vaksman, Zalman
AU - Hakonarson, Hakon
AU - Diskin, Sharon J.
AU - Metayer, Catherine
AU - Claus, Elizabeth B.
AU - Il’yasova, Dora
AU - Walsh, Kyle M.
AU - Schildkraut, Joellen
AU - Barnholtz-Sloan, Jill S.
AU - Olson, Sara H.
AU - Bernstein, Jonine L.
AU - Johansen, Christoffer
AU - Jenkins, Robert B.
AU - Melin, Beatrice S.
AU - Wrensch, Margaret R.
AU - Houlston, Richard S.
AU - Taylor, Michael D.
AU - Wiemels, Joseph L.
AU - Bondy, Melissa L.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Ependymoma
KW - Mendelian randomization
KW - Pediatric cancer
KW - Telomere length
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U2 - 10.1186/s40478-020-01038-w
DO - 10.1186/s40478-020-01038-w
M3 - Article
C2 - 33115534
AN - SCOPUS:85094856089
SN - 2051-5960
VL - 8
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
IS - 1
M1 - 173
ER -