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

2014; Nature Portfolio; Volume: 46; Issue: 7 Linguagem: Inglês

10.1038/ng.3004

1546-1718

Kyle M. Walsh, Veryan Codd, Ivan Smirnov, Terri Rice, Paul A. Decker, Helen M. Hansen, Thomas M. Kollmeyer, Matthew Kosel, Annette M. Molinaro, Lucie McCoy, Paige M. Bracci, B. S. Cabriga, Melike Pekmezci, Shichun Zheng, Joseph L. Wiemels, Alexander R. Pico, Tarık Tihan, Mitchel S. Berger, Susan M. Chang, Michael D. Prados, Daniel H. Lachance, Brian Patrick O’Neill, Hugues Sicotte, Jeanette E. Eckel‐Passow, Pim van der Harst, John K. Wiencke, Nilesh J. Samani, Robert B. Jenkins, Margaret Wrensch,

Mitochondrial Function and Pathology

Kyle Walsh and colleagues identify a variant near TERC associated with glioma susceptibility. They further show that glioma risk alleles near TERC and TERT are associated with longer mean telomere length in leukocytes, implicating telomerase activity in gliomagenesis. 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)1. 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.