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Walsh, K.M.* ; Codd, V.* ; Rice, T.* ; Nelson, C.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.* ; Samani, N.J.* ; Wiencke, J.K.* ; Wrensch, M.R.* ; ENGAGE Consortium Telomere Group (Albrecht, E. ; Gieger, C. ; Klopp, N. ; Peters, A. ; Wichmann, H.-E.)

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk.

Oncotarget 6, 42468-42477 (2015)

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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 genotypicallyestimated 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Single Nucleotide Polymorphism ; Telomerase ; Telomere ; Cst Complex ; Glioma; Genome-wide Association; Tert Promoter Mutations; Mendelian Randomization; Cancer-risk; Older Age; Variants; Disease; Genes; Susceptibility; Metaanalysis

ISSN (print) / ISBN 1949-2553

e-ISSN 1949-2553

Journal OncoTarget

Quellenangaben Volume: 6, Issue: 40, Pages: 42468-42477

Publisher Impact Journals LLC

Publishing Place Albany

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)
Institute of Epidemiology (EPI)