title: Cancer susceptibility variants and the risk of adult glioma in a US case-control study.
abstract: Malignant gliomas are the most common and deadly brain tumors. Although their etiology remains elusive, recent studies have narrowed the search for genetic loci that influence risk. We examined variants implicated in recent cancer genome-wide association studies (GWAS) for associations with glioma risk in a US case-control study. Cases were identified from neurosurgical and neuro-oncology clinics at major academic centers in the Southeastern US. Controls were identified from the community or were friends or other associates of cases. We examined a total of 191 susceptibility variants in genes identified in published cancer GWAS including glioma. A total of 639 glioma cases and 649 controls, all Caucasian, were included in analysis. Cases were enrolled a median of 1 month following diagnosis. Among glioma GWAS-identified variants, we detected associations in CDKN2B, RTEL1, TERT and PHLDB1, whereas we did not find overall associations for CCDC26. Results showed clear heterogeneity according to histologic subtypes of glioma, with TERT and RTEL variants a feature of astrocytic tumors and glioblastoma (GBM), CCDC26 and PHLDB1 variants a feature of astrocytic and oligodendroglial tumors, and CDKN2B variants most prominent in GBM. No examined variant in other cancer GWAS was found to be related to risk after adjustment for multiple comparisons. These results suggest that GWAS-identified SNPs in glioma mark different molecular etiologies in glioma. Stratification by broad histological subgroups may shed light on molecular mechanisms and assist in the discovery of novel loci in future studies of genetic susceptibility variants in glioma.
authors.affiliation: Department of Cancer Epidemiology & Genetics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. kathleen.egan@moffitt.org
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Egan
authors.forename: Reid C
authors.initials: RC
authors.lastname: Thompson
authors.forename: L B
authors.initials: LB
authors.lastname: Nabors
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.forename: Renato V
authors.initials: RV
authors.lastname: Larocca
authors.forename: Steven
authors.initials: S
authors.lastname: Brem
authors.forename: Paul L
authors.initials: PL
authors.lastname: Moots
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Madden
authors.forename: James E
authors.initials: JE
authors.lastname: Browning
authors.forename: Y
authors.initials: Y
authors.lastname: Ann Chen
mesh_terms: D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005910:Glioma / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D012307:Risk Factors; D014481:United States / Q000453:epidemiology