title: SSBP2 variants are associated with survival in glioblastoma patients.
abstract: OBJECTIVE
  Glioblastoma is a devastating, incurable disease with few known prognostic factors. Here, we present the first genome-wide survival and validation study for glioblastoma.
  
  
  METHODS
  Cox regressions for survival with 314,635 inherited autosomal single-nucleotide polymorphisms (SNP) among 315 San Francisco Adult Glioma Study patients for discovery and three independent validation data sets [87 Mayo Clinic, 232 glioma patients recruited from several medical centers in Southeastern United States (GliomaSE), and 115 The Cancer Genome Atlas patients] were used to identify SNPs associated with overall survival for Caucasian glioblastoma patients treated with the current standard of care, resection, radiation, and temozolomide (total n = 749). Tumor expression of the gene that contained the identified prognostic SNP was examined in three separate data sets (total n = 619). Genotype imputation was used to estimate hazard ratios (HR) for SNPs that had not been directly genotyped.
  
  
  RESULTS
  From the discovery and validation analyses, we identified a variant in single-stranded DNA-binding protein 2 (SSBP2) on 5q14.1 associated with overall survival in combined analyses (HR, 1.64; P = 1.3 × 10(-6)). Expression of SSBP2 in tumors from three independent data sets also was significantly related to patient survival (P = 5.3 × 10(-4)). Using genotype imputation, the SSBP2 SNP rs17296479 had the strongest statistically significant genome-wide association with poorer overall patient survival (HR, 1.79; 95% CI, 1.45-2.22; P = 1.0 × 10(-7)).
  
  
  CONCLUSIONS
  The minor allele of SSBP2 SNP rs17296479 and the increased tumor expression of SSBP2 were statistically significantly associated with poorer overall survival among glioblastoma patients. With further confirmation, previously unrecognized inherited variations influencing survival may warrant inclusion in clinical trials to improve randomization. Unaccounted for genetic influence on survival could produce unwanted bias in such studies.
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco 185 Berry St, Suite 5700, San Francisco, CA 94107, USA. yuanyuan.xiao@ucsf.edu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.forename: Terri
authors.initials: T
authors.lastname: Rice
authors.forename: Lucie S
authors.initials: LS
authors.lastname: McCoy
authors.forename: Ivan
authors.initials: I
authors.lastname: Smirnov
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Patoka
authors.forename: Helen M
authors.initials: HM
authors.lastname: Hansen
authors.forename: Joe L
authors.initials: JL
authors.lastname: Wiemels
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Kosel
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lachance
authors.forename: Brian Patrick
authors.initials: BP
authors.lastname: O'Neill
authors.forename: Jan C
authors.initials: JC
authors.lastname: Buckner
authors.forename: Reid C
authors.initials: RC
authors.lastname: Thompson
authors.forename: Louis Burt
authors.initials: LB
authors.lastname: Nabors
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
authors.forename: Steve
authors.initials: S
authors.lastname: Brem
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Madden
authors.forename: James E
authors.initials: JE
authors.lastname: Browning
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Egan
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D004268:DNA-Binding Proteins / Q000235:genetics*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D055106:Genome-Wide Association Study; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D000077204:Temozolomide
chemical_list: D004268:DNA-Binding Proteins; C477058:SSBP2 protein, human; D003606:Dacarbazine; D000077204:Temozolomide