Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.
Journal Article (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
- PMC4074274
Electronic International Standard Serial Number (EISSN)
- 1546-1718
Digital Object Identifier (DOI)
- 10.1038/ng.3004
Language
- eng
Conference Location
- United States