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Title: Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk
Authors: Walsh, K. M.
Codd, Veryan
Rice, T.
Nelson, Christopher P.
Smirnov, I. V.
McCoy, L. S.
Hansen, H. M.
Elhauge, E.
Ojha, J.
Francis, S. S.
Madsen, N. R.
Bracci, P. M.
Pico, A. R.
Molinaro, A. M.
Tihan, T.
Berger, M. S.
Chang, S. M.
Prados, M. D.
Jenkins, R. B.
Wiemels, J. L.
ENGAGE Consortium Telomere Group
Samani, Nilesh Jayantilal
Wiencke, J. K.
Wrensch, M. R.
First Published: 4-Dec-2015
Publisher: Impact Journals
Citation: Oncotarget, 2015, 6 (40), pp. 42468-42477
Abstract: Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82x10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48x10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83x10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.
DOI Link: 10.18632/oncotarget.6468
eISSN: 1949-2553
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015, the authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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