Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies

Details

• Alternative Title:
  Genet Epidemiol
• Personal Author:
  Walsh, Kyle M. ; Anderson, Erik ; Hansen, Helen M. ; Decker, Paul A. ; Kosel, Matt L. ; Kollmeyer, Thomas ; Rice, Terri ; Zheng, Shichun ; Xiao, Yuanyuan ; Chang, Jeffrey S. ; McCoy, Lucie S. ; Bracci, Paige M. ; Wiemels, Joe L. ; Pico, Alexander R. ; Smirnov, Ivan ; Lachance, Daniel H. ; Sicotte, Hugues ; Eckel-Passow, Jeanette E. ; Wiencke, John K. ; Jenkins, Robert B. ; Wrensch, Margaret R.
• Description:
  Genomewide association studies (GWAS) and candidate-gene studies have implicated single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded variable results and few genetic risk factors have been consistently replicated. We conducted a case-control study of Caucasian glioma cases and controls from the University of California San Francisco (810 cases, 512 controls) and the Mayo Clinic (852 cases, 789 controls) in an attempt to replicate previously reported genetic risk factors for glioma. Sixty SNPs selected from the literature (eight from GWAS and 52 from candidate-gene studies) were successfully genotyped on an Illumina custom genotyping panel. Eight SNPs in/near seven different genes (TERT, EGFR, CCDC26, CDKN2A, PHLDB1, RTEL1, TP53) were significantly associated with glioma risk in the combined dataset (P < 0.05), with all associations in the same direction as in previous reports. Several SNP associations showed considerable differences across histologic subtype. All eight successfully replicated associations were first identified by GWAS, although none of the putative risk SNPs from candidate-gene studies was associated in the full case-control sample (all P values > 0.05). Although several confirmed associations are located near genes long known to be involved in gliomagenesis (e.g., EGFR, CDKN2A, TP53), these associations were first discovered by the GWAS approach and are in noncoding regions. These results highlight that the deficiencies of the candidate-gene approach lay in selecting both appropriate genes and relevant SNPs within these genes.
• Subjects:
  Aged Case-Control Studies Central Nervous System Neoplasms DNA Helicases ErbB Receptors Female Genes, P16 Genes, P53 Genetic Predisposition To Disease Genome-Wide Association Study Glioma Humans Intracellular Signaling Peptides And Proteins Male Middle Aged Nerve Tissue Proteins Polymorphism, Single Nucleotide Telomerase White People

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• Source:
  Genet Epidemiol. 2012; 37(2):222-228
• Pubmed ID:
  23280628
• Pubmed Central ID:
  PMC3670948
• Document Type:
  Journal Article
• Funding:
  P50 CA108961/CA/NCI NIH HHS/United States ; HHSN261201000035C/CA/NCI NIH HHS/United States ; RC1 NS068222/NS/NINDS NIH HHS/United States ; RC1NS068222Z/NS/NINDS NIH HHS/United States ; R25 CA112355/CA/NCI NIH HHS/United States ; HHSN261201000036C/CA/NCI NIH HHS/United States ; U58 DP000807/DP/NCCDPHP CDC HHS/United States ; 1U58 DP000807-01/DP/NCCDPHP CDC HHS/United States ; P50 CA097257/CA/NCI NIH HHS/United States ; R25CA112355/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; HHSN261201000035I/CA/NCI NIH HHS/United States ; P50CA097257/CA/NCI NIH HHS/United States ; HHSN261201000034C/CA/NCI NIH HHS/United States ; P50CA108961/CA/NCI NIH HHS/United States ; R01CA52689/CA/NCI NIH HHS/United States ; P30 CA15083/CA/NCI NIH HHS/United States ; R01 CA052689/CA/NCI NIH HHS/United States
• Place as Subject:
  California
• Volume:
  37
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:4e456259182ab39c8dbcb70b65cb31bed4ab79732dc14563a16cebacf14ffb05
• Download URL:
  https://stacks.cdc.gov/view/cdc/33575/cdc_33575_DS1.pdf
• File Type:
  [PDF - 297.73 KB ]