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

被引：156

作者：

Walsh, Kyle M. ^{[1
,2
]}

Codd, Veryan ^{[3
,4
]}

Smirnov, Ivan V. ^{[5
]}

Rice, Terri ^{[1
]}

Decker, Paul A. ^{[6
]}

Hansen, Helen M. ^{[1
]}

Kollmeyer, Thomas ^{[7
]}

Kosel, Matthew L. ^{[6
]}

Molinaro, Annette M. ^{[5
]}

McCoy, Lucie S. ^{[1
]}

Bracci, Paige M. ^{[8
]}

Cabriga, Belinda S. ^{[1
]}

Pekmezci, Melike ^{[9
]}

Zheng, Shichun ^{[1
]}

Wiemels, Joseph L. ^{[1
,8
,10
]}

Pico, Alexander R. ^{[1
,11
]}

Tihan, Tarik ^{[9
]}

Berger, Mitchell S. ^{[5
]}

Chang, Susan M. ^{[5
]}

Prados, Michael D. ^{[5
]}

Lachance, Daniel H. ^{[12
]}

O'Neill, Brain Patrick ^{[12
]}

Sicotte, Hugues ^{[6
]}

Eckel-Passow, Jeanette E. ^{[6
]}

van der Harst, Pim ^{[13
,14
]}

Wiencke, John K. ^{[1
,10
]}

Samani, Nilesh J. ^{[3
,4
]}

Jenkins, Robert B. ^{[7
]}

Wrensch, Margaret R. ^{[1
,10
]}

机构：

[1] Univ Calif San Francisco, Dept Neurol Surg, Div Neuroepidemiol, San Francisco, CA 94132 USA

[2] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Program Canc Genet, San Francisco, CA USA

[3] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England

[4] Glenfield Hosp, Nat Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England

[5] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[6] Mayo Clin, Coll Med, Div Biomed Stat & Informat, Rochester, MN USA

[7] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA

[8] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[9] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA

[10] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA USA

[11] Gladstone Inst, Dept Bioinformat, San Francisco, CA USA

[12] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA

[13] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[14] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

来源：

NATURE GENETICS | 2014年 / 46卷 / 07期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; PROMOTER MUTATIONS; CARDIOVASCULAR-DISEASE; COLORECTAL-CANCER; GLIOBLASTOMA; METAANALYSIS; PATHWAYS; MELANOMA; HUMANS;

D O I：

10.1038/ng.3004

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 (P-combined = 8.3 x 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 x 10(-20) and 4.4 x 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.

引用

页码：731 / 735

页数：5

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