title: Investigation of established genetic risk variants for glioma in prediagnostic samples from a population-based nested case-control study.
abstract: BACKGROUND
  Although glioma etiology is poorly understood in general, growing evidence indicates a genetic component. Four large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case-control design, where cases have been recruited at the time of or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included.
  
  
  METHODS
  To confirm glioma risk variants in a prospective setting, we have analyzed 11 previously identified risk variants in a set of prediagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population-based biobank reserved for cancer research.
  
  
  RESULTS
  We confirmed the association with glioma risk for variants within five genomic regions: 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study.
  
  
  CONCLUSIONS
  Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk and may, consequently, affect gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants or markers for glioma prognosis.
  
  
  CONCLUSIONS
  Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus etiology.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. Computational Life Science Cluster (CLiC), Umeå University, Umeå, Sweden. carl.wibom@onkologi.umu.se.
authors.forename: Carl
authors.initials: C
authors.lastname: Wibom
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: Florentin
authors.initials: F
authors.lastname: Späth
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. Computational Life Science Cluster (CLiC), Umeå University, Umeå, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Dahlin
authors.affiliation: Cancer Registry of Norway, Institute of Population-Based Cancer Research, Department of Research, Oslo, Norway.
authors.forename: Hilde
authors.initials: H
authors.lastname: Langseth
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. Department of Informatics, University of Oslo, Oslo, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Hovig
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
authors.forename: Preetha
authors.initials: P
authors.lastname: Rajaraman
authors.affiliation: Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
authors.forename: Tom Børge
authors.initials: TB
authors.lastname: Johannesen
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Melin
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D004265:DNA Helicases / Q000235:genetics; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005910:Glioma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D062085:RNA, Long Noncoding / Q000235:genetics; D012042:Registries; D012307:Risk Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: C561518:CDKN2B antisense RNA, human; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C487973:PHLDB1 protein, human; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; C000613877:long noncoding RNA CCDC26, human; C532890:RTEL1 protein, human; D004265:DNA Helicases