Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.

Published

Journal Article

Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined = 8.3 × 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma and replication data (1,644 cases and 7,736 controls). This region has previously been associated with mean leukocyte telomere length (LTL). We therefore examined the relationship between LTL and both this new risk locus and other previously established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684 individuals). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 × 10(-20) and 4.4 × 10(-19), respectively). In contrast, risk-associated alleles near RTEL1 were inconsistently associated with LTL, suggesting the presence of distinct causal alleles. No other risk loci for glioma were associated with LTL. The identification of risk alleles for glioma near TERC and TERT that also associate with telomere length implicates telomerase in gliomagenesis.

Full Text

Duke Authors

Cited Authors

  • Walsh, KM; Codd, V; Smirnov, IV; Rice, T; Decker, PA; Hansen, HM; Kollmeyer, T; Kosel, ML; Molinaro, AM; McCoy, LS; Bracci, PM; Cabriga, BS; Pekmezci, M; Zheng, S; Wiemels, JL; Pico, AR; Tihan, T; Berger, MS; Chang, SM; Prados, MD; Lachance, DH; O'Neill, BP; Sicotte, H; Eckel-Passow, JE; ENGAGE Consortium Telomere Group, ; van der Harst, P; Wiencke, JK; Samani, NJ; Jenkins, RB; Wrensch, MR

Published Date

  • July 2014

Published In

Volume / Issue

  • 46 / 7

Start / End Page

  • 731 - 735

PubMed ID

  • 24908248

Pubmed Central ID

  • 24908248

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.3004

Language

  • eng