Skip to main content

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

Publication ,  Journal Article
Walsh, KM; Codd, V; Rice, T; Nelson, CP; Smirnov, IV; McCoy, LS; Hansen, HM; Elhauge, E; Ojha, J; Francis, SS; Madsen, NR; Bracci, PM ...
Published in: Oncotarget
December 15, 2015

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.

Duke Scholars

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

December 15, 2015

Volume

6

Issue

40

Start / End Page

42468 / 42477

Location

United States

Related Subject Headings

  • Telomere
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Models, Statistical
  • Male
  • Leukocytes
  • Humans
  • Glioma
  • Genotype
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Walsh, K. M., Codd, V., Rice, T., Nelson, C. P., Smirnov, I. V., McCoy, L. S., … Wrensch, M. R. (2015). Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk. Oncotarget, 6(40), 42468–42477. https://doi.org/10.18632/oncotarget.6468
Walsh, Kyle M., Veryan Codd, Terri Rice, Christopher P. Nelson, Ivan V. Smirnov, Lucie S. McCoy, Helen M. Hansen, et al. “Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk.Oncotarget 6, no. 40 (December 15, 2015): 42468–77. https://doi.org/10.18632/oncotarget.6468.
Walsh KM, Codd V, Rice T, Nelson CP, Smirnov IV, McCoy LS, et al. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk. Oncotarget. 2015 Dec 15;6(40):42468–77.
Walsh, Kyle M., et al. “Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk.Oncotarget, vol. 6, no. 40, Dec. 2015, pp. 42468–77. Pubmed, doi:10.18632/oncotarget.6468.
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. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk. Oncotarget. 2015 Dec 15;6(40):42468–42477.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

December 15, 2015

Volume

6

Issue

40

Start / End Page

42468 / 42477

Location

United States

Related Subject Headings

  • Telomere
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Models, Statistical
  • Male
  • Leukocytes
  • Humans
  • Glioma
  • Genotype
  • Genome-Wide Association Study