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Nat Genet. 2014 Jul;46(7):731-5. doi: 10.1038/ng.3004. Epub 2014 Jun 8.

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

Author information

1
1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
2
1] Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
3
Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
4
Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
5
Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
6
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
7
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
8
Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
9
1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. [3] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
10
1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Department of Bioinformatics, Gladstone Institutes, San Francisco, California, USA.
11
Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
12
1] Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [2] Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
13
1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.

Abstract

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.

PMID:
24908248
PMCID:
PMC4074274
DOI:
10.1038/ng.3004
[Indexed for MEDLINE]
Free PMC Article

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