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Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis.

Publication ,  Journal Article
Walsh, KM; Rice, T; Decker, PA; Kosel, ML; Kollmeyer, T; Hansen, HM; Zheng, S; McCoy, LS; Bracci, PM; Anderson, E; Hsuang, G; Wiemels, JL ...
Published in: Neuro Oncol
August 2013

BACKGROUND: Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma. METHODS: SNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between "number of risk alleles" and "age at diagnosis," adjusted for sex and study site and stratified by tumor grade/histology where appropriate. RESULTS: Four SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10(-22) and P = 9.5 × 10(-7), respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10(-4) and P = 2.5 × 10(-4), respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups. CONCLUSIONS: Carrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres).

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Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

August 2013

Volume

15

Issue

8

Start / End Page

1041 / 1047

Location

England

Related Subject Headings

  • Telomerase
  • Risk Factors
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Grading
  • Middle Aged
  • Male
  • Humans
  • Glioma
 

Citation

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MLA
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Walsh, K. M., Rice, T., Decker, P. A., Kosel, M. L., Kollmeyer, T., Hansen, H. M., … Wrensch, M. R. (2013). Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis. Neuro Oncol, 15(8), 1041–1047. https://doi.org/10.1093/neuonc/not051
Walsh, Kyle M., Terri Rice, Paul A. Decker, Matthew L. Kosel, Thomas Kollmeyer, Helen M. Hansen, Shichun Zheng, et al. “Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis.Neuro Oncol 15, no. 8 (August 2013): 1041–47. https://doi.org/10.1093/neuonc/not051.
Walsh KM, Rice T, Decker PA, Kosel ML, Kollmeyer T, Hansen HM, et al. Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis. Neuro Oncol. 2013 Aug;15(8):1041–7.
Walsh, Kyle M., et al. “Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis.Neuro Oncol, vol. 15, no. 8, Aug. 2013, pp. 1041–47. Pubmed, doi:10.1093/neuonc/not051.
Walsh KM, Rice T, Decker PA, Kosel ML, Kollmeyer T, Hansen HM, Zheng S, McCoy LS, Bracci PM, Anderson E, Hsuang G, Wiemels JL, Pico AR, Smirnov I, Molinaro AM, Tihan T, Berger MS, Chang SM, Prados MD, Lachance DH, Sicotte H, Eckel-Passow JE, Wiencke JK, Jenkins RB, Wrensch MR. Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis. Neuro Oncol. 2013 Aug;15(8):1041–1047.
Journal cover image

Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

August 2013

Volume

15

Issue

8

Start / End Page

1041 / 1047

Location

England

Related Subject Headings

  • Telomerase
  • Risk Factors
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Grading
  • Middle Aged
  • Male
  • Humans
  • Glioma