SSBP2 variants are associated with survival in glioblastoma patients
Published Date:Apr 03 2012
Source:Clin Cancer Res. 18(11):3154-3162.
Pubmed Central ID:PMC3607457
Funding:1U58 DP000807-01/DP/NCCDPHP CDC HHS/United States
CAR01116174/PHS HHS/United States
HHSN261201000034C/PHS HHS/United States
HHSN261201000035C/PHS HHS/United States
HHSN261201000036C/PHS HHS/United States
P30 CA15083/CA/NCI NIH HHS/United States
P50 CA097257/CA/NCI NIH HHS/United States
P50 CA108961/CA/NCI NIH HHS/United States
P50CA097257/CA/NCI NIH HHS/United States
P50CA108961/CA/NCI NIH HHS/United States
R01 CA052689/CA/NCI NIH HHS/United States
R01 CA116174/CA/NCI NIH HHS/United States
R01CA52689/CA/NCI NIH HHS/United States
Glioblastoma is a devastating, incurable disease with few known prognostic factors. Here we present the first genome-wide survival and validation study for glioblastoma.
Cox regressions for survival with 314,635 inherited autosomal single nucleotide polymorphisms (SNPs) among 315 San Francisco Adult Glioma Study patients for discovery and three independent validation datasets (87 Mayo Clinic, 232 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 datasets (total n=619). Genotype imputation was used to estimate hazard ratios (HRs) for SNPs that had not been directly genotyped.
From the discovery and validation analyses, we identified a variant in SSBP2 (single-stranded DNA-binding protein 2) on 5q14.1 associated with overall survival in combined analyses (hazard ratio (HR) = 1.64; P = 1.3X10−6). Expression of SSBP2 in tumors from three independent datasets also was significantly related to patient survival (P = 5.3 X 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 X 10−7).
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.
application/vnd.openxmlformats-officedocument.presentationml.presentation application/vnd.ms-excel text/plain image/gif image/jpeg image/gif image/jpeg image/gif image/jpeg image/gif image/jpeg
You May Also Like: