title: Genome-wide association study of glioma and meta-analysis.
abstract: Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. rajarama@mail.nih.gov
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mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019098:Telomerase / Q000235:genetics
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; C509186:TERT protein, human; D019098:Telomerase; C532890:RTEL1 protein, human; D004265:DNA Helicases