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

Details

• Alternative Title:
  Nat Genet
• Personal Author:
  Walsh, Kyle M. ; Codd, Veryan ; Smirnov, Ivan V. ; Rice, Terri ; Decker, Paul A. ; Hansen, Helen M. ; Kollmeyer, Thomas ; Kosel, Matthew L. ; Molinaro, Annette M. ; McCoy, Lucie S. ; Bracci, Paige M. ; Cabriga, Belinda S. ; Pekmezci, Melike ; Zheng, Shichun ; Wiemels, Joseph L. ; Pico, Alexander R. ; Tihan, Tarik ; Berger, Mitchell S. ; Chang, Susan M. ; Prados, Michael D. ; Lachance, Daniel H. ; O’Neill, Brian P. ; Sicotte, Hugues ; Eckel-Passow, Jeanette E. ; van der Harst, Pim ; Wiencke, John K. ; Samani, Nilesh J. ; Jenkins, Robert B. ; Wrensch, Margaret R.
• Corporate Authors:
  ENGAGE Consortium Telomere Group
• Description:
  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.
• Keywords:
  Adult Case-Control Studies Genome-Wide Association Study Genotype Glioma Humans Leukocytes Neoplasm Grading Polymorphism, Single Nucleotide Prognosis Risk Factors RNA RTEL1 Single Nucleotide Polymorphism Telomerase Telomere TERC TERT

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• Source:
  Nat Genet. 46(7):731-735
• Pubmed ID:
  24908248
• Pubmed Central ID:
  PMC4074274
• Document Type:
  Journal Article
• Funding:
  R01 CA139020/CA/NCI NIH HHSUnited States/ ; R01CA126831/CA/NCI NIH HHSUnited States/ ; U58DP003862-01/DP/NCCDPHP CDC HHSUnited States/ ; HHSN261201000140C/CA/NCI NIH HHSUnited States/ ; P50 CA108961/CA/NCI NIH HHSUnited States/ ; HHSN261201000035C/CA/NCI NIH HHSUnited States/ ; RC1NS068222Z/NS/NINDS NIH HHSUnited States/ ; R25 CA112355/CA/NCI NIH HHSUnited States/ ; R01 CA126831/CA/NCI NIH HHSUnited States/ ; UL1 RR024131/RR/NCRR NIH HHSUnited States/ ; P50 CA097257/CA/NCI NIH HHSUnited States/ ; UL1RR024131/RR/NCRR NIH HHSUnited States/ ; P30CA15083/CA/NCI NIH HHSUnited States/ ; UL1 TR000004/TR/NCATS NIH HHSUnited States/ ; R01 CA052689/CA/NCI NIH HHSUnited States/ ; BHF_/British Heart FoundationUnited Kingdom/ ; RC1 NS068222/NS/NINDS NIH HHSUnited States/ ; R25CA112355/CA/NCI NIH HHSUnited States/ ; P30 CA015083/CA/NCI NIH HHSUnited States/ ; HHSN261201000035I/CA/NCI NIH HHSUnited States/ ; P50CA097257/CA/NCI NIH HHSUnited States/ ; HHSN261201000034C/CA/NCI NIH HHSUnited States/ ; P50CA108961/CA/NCI NIH HHSUnited States/ ; R01CA139020/CA/NCI NIH HHSUnited States/ ; R01CA52689/CA/NCI NIH HHSUnited States/ ; U58 DP003862/DP/NCCDPHP CDC HHSUnited States/ ; WT_/Wellcome TrustUnited Kingdom/
• Volume:
  46
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:45765e42f289c0e5d9139347b081a9f52330b6eaab7d0e44c7f22e6c6d4da3e7
• Download URL:
  https://stacks.cdc.gov/view/cdc/27881/cdc_27881_DS1.pdf
• File Type:
  [PDF - 632.83 KB ]