title: SWI/SNF gene variants and glioma risk and outcome.
abstract: BACKGROUND
  The human SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays essential roles in a variety of cellular processes and has been implicated in human cancer. However, the role of germline genetic variants in this complex in relation to cancer risk is not well studied.
  
  
  METHODS
  We assessed the association of 16 variants in the catalytic subunits (SMARCA2 and SMARCA4) of the SWI/SNF complex with the risk of glioma subtypes (lower grade astrocytoma, oligodendroglioma and glioblastoma [GBM]) and with mortality from high-grade tumors (GBM) in a multicenter US case-control study that included 561 cases and 574 controls. Associations were estimated with odds ratios (OR, for risk) or hazards ratios (HR, for mortality) with 95% confidence intervals (CI). False discovery rate (FDR-q) was used to control for multiple testing in risk associations.
  
  
  RESULTS
  None of the investigated SNPs was associated with overall glioma risk. However, analyses according to histological subtypes revealed a statistically significant increased risk of oligodendroglioma in association with SMARCA2 rs2296212 (OR = 4.05, 95% CI = 1.11-14.80, P = 0.030, q = 0.08) and rs4741651 (OR = 4.68, 95% CI = 1.43-15.30, P = 0.011, q = 0.08) and SMARCA4 rs11672232 (OR = 1.90, 95% CI = 1.01-3.58, P = 0.048, q = 0.08) and rs12232780 (OR = 2.14, 95% CI = 1.06-4.33, P = 0.035, q = 0.08). No significant risk associations were observed for GBM or lower grade astrocytoma. Suggestive associations with GBM mortality were not validated in the Cancer Genome Atlas.
  
  
  CONCLUSIONS
  Our findings suggest that genetic variants in SMARCA2 and SMARCA4 influence the risk of oligodendroglioma. Further research is warranted on the SWI/SNF complex genes and epigenetic mechanisms more generally in the development of glioma in adults.
authors.affiliation: Department of Cancer Epidemiology & Genetics, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. ernest.amankwah@moffitt.org
authors.forename: Ernest K
authors.initials: EK
authors.lastname: Amankwah
authors.forename: Reid C
authors.initials: RC
authors.lastname: Thompson
authors.forename: L Burton
authors.initials: LB
authors.lastname: Nabors
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
authors.forename: James E
authors.initials: JE
authors.lastname: Browning
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Madden
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Egan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000145:classification / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D016022:Case-Control Studies; D004265:DNA Helicases / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D005910:Glioma / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics*; D009837:Oligodendroglioma / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases