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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Walsh, KM; Codd, V; Rice, T; Nelson, CP; Smirnov, IV; McCoy, LS; Hansen, HM; Elhauge, E; Ojha, J; Francis, SS; Madsen, NR; Bracci, PM; Pico, AR; Molinaro, AM; Tihan, T; Berger, MS; Chang, SM; Prados, MD; Jenkins, RB; Wiemels, JL; ENGAGE Consortium Telomere Group, ; Samani, NJ; Wiencke, JK; Wrensch, MR

Published Date

  • December 2015

Published In

Volume / Issue

  • 6 / 40

Start / End Page

  • 42468 - 42477

PubMed ID

  • 26646793

Pubmed Central ID

  • 26646793

Electronic International Standard Serial Number (EISSN)

  • 1949-2553

International Standard Serial Number (ISSN)

  • 1949-2553

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.6468

Language

  • eng