SSBP2 variants are associated with survival in glioblastoma patients

Yuanyuan Xiao; Paul A. Decker; Terri Rice; Lucie S. McCoy; Ivan Smirnov; Joseph S. Patoka; Helen M. Hansen; Joe L. Wiemels; Tarik Tihan; Michael D. Prados; Susan M. Chang; Mitchel S. Berger; Matthew L. Kosel; Brooke L. Fridley; Daniel H. Lachance; Brian Patrick O'Neill; Jan C. Buckner; Reid C. Thompson; Louis Burt Nabors; Jeffrey J. Olson; Steve Brem; Melissa H. Madden; James E. Browning; John K. Wiencke; Kathleen M. Egan; Robert B. Jenkins; Margaret R. Wrensch

doi:10.1158/1078-0432.CCR-11-2778

SSBP2 variants are associated with survival in glioblastoma patients

Yuanyuan Xiao, Paul A. Decker, Terri Rice, Lucie S. McCoy, Ivan Smirnov, Joseph S. Patoka, Helen M. Hansen, Joe L. Wiemels, Tarik Tihan, Michael D. Prados, Susan M. Chang, Mitchel S. Berger, Matthew L. Kosel, Brooke L. Fridley, Daniel H. Lachance, Brian Patrick O'Neill, Jan C. Buckner, Reid C. Thompson, Louis Burt Nabors, Jeffrey J. OlsonSteve Brem, Melissa H. Madden, James E. Browning, John K. Wiencke, Kathleen M. Egan, Robert B. Jenkins, Margaret R. Wrensch

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Abstract

Purpose: Glioblastoma is a devastating, incurable disease with few known prognostic factors. Here, we present the first genome-wide survival and validation study for glioblastoma. Experimental Design: 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 DNAbinding 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). Conclusion: 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.

Original language	English (US)
Pages (from-to)	3154-3162
Number of pages	9
Journal	Clinical Cancer Research
Volume	18
Issue number	11
DOIs	https://doi.org/10.1158/1078-0432.CCR-11-2778
State	Published - Jun 1 2012

ASJC Scopus subject areas

General Medicine

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10.1158/1078-0432.CCR-11-2778

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Xiao, Y., Decker, P. A., Rice, T., McCoy, L. S., Smirnov, I., Patoka, J. S., Hansen, H. M., Wiemels, J. L., Tihan, T., Prados, M. D., Chang, S. M., Berger, M. S., Kosel, M. L., Fridley, B. L., Lachance, D. H., O'Neill, B. P., Buckner, J. C., Thompson, R. C., Nabors, L. B., ... Wrensch, M. R. (2012). SSBP2 variants are associated with survival in glioblastoma patients. Clinical Cancer Research, 18(11), 3154-3162. https://doi.org/10.1158/1078-0432.CCR-11-2778

Xiao, Y, Decker, PA, Rice, T, McCoy, LS, Smirnov, I, Patoka, JS, Hansen, HM, Wiemels, JL, Tihan, T, Prados, MD, Chang, SM, Berger, MS, Kosel, ML, Fridley, BL, Lachance, DH , O'Neill, BP, Buckner, JC, Thompson, RC, Nabors, LB, Olson, JJ, Brem, S, Madden, MH, Browning, JE, Wiencke, JK, Egan, KM, Jenkins, RB & Wrensch, MR 2012, 'SSBP2 variants are associated with survival in glioblastoma patients', Clinical Cancer Research, vol. 18, no. 11, pp. 3154-3162. https://doi.org/10.1158/1078-0432.CCR-11-2778

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title = "SSBP2 variants are associated with survival in glioblastoma patients",

abstract = "Purpose: Glioblastoma is a devastating, incurable disease with few known prognostic factors. Here, we present the first genome-wide survival and validation study for glioblastoma. Experimental Design: 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 DNAbinding 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). Conclusion: 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.",

author = "Yuanyuan Xiao and Decker, {Paul A.} and Terri Rice and McCoy, {Lucie S.} and Ivan Smirnov and Patoka, {Joseph S.} and Hansen, {Helen M.} and Wiemels, {Joe L.} and Tarik Tihan and Prados, {Michael D.} and Chang, {Susan M.} and Berger, {Mitchel S.} and Kosel, {Matthew L.} and Fridley, {Brooke L.} and Lachance, {Daniel H.} and O'Neill, {Brian Patrick} and Buckner, {Jan C.} and Thompson, {Reid C.} and Nabors, {Louis Burt} and Olson, {Jeffrey J.} and Steve Brem and Madden, {Melissa H.} and Browning, {James E.} and Wiencke, {John K.} and Egan, {Kathleen M.} and Jenkins, {Robert B.} and Wrensch, {Margaret R.}",

year = "2012",

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doi = "10.1158/1078-0432.CCR-11-2778",

language = "English (US)",

volume = "18",

pages = "3154--3162",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

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TY - JOUR

T1 - SSBP2 variants are associated with survival in glioblastoma patients

AU - Xiao, Yuanyuan

AU - Decker, Paul A.

AU - Rice, Terri

AU - McCoy, Lucie S.

AU - Smirnov, Ivan

AU - Patoka, Joseph S.

AU - Hansen, Helen M.

AU - Wiemels, Joe L.

AU - Tihan, Tarik

AU - Prados, Michael D.

AU - Chang, Susan M.

AU - Berger, Mitchel S.

AU - Kosel, Matthew L.

AU - Fridley, Brooke L.

AU - Lachance, Daniel H.

AU - O'Neill, Brian Patrick

AU - Buckner, Jan C.

AU - Thompson, Reid C.

AU - Nabors, Louis Burt

AU - Olson, Jeffrey J.

AU - Brem, Steve

AU - Madden, Melissa H.

AU - Browning, James E.

AU - Wiencke, John K.

AU - Egan, Kathleen M.

AU - Jenkins, Robert B.

AU - Wrensch, Margaret R.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Purpose: Glioblastoma is a devastating, incurable disease with few known prognostic factors. Here, we present the first genome-wide survival and validation study for glioblastoma. Experimental Design: 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 DNAbinding 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). Conclusion: 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.

AB - Purpose: Glioblastoma is a devastating, incurable disease with few known prognostic factors. Here, we present the first genome-wide survival and validation study for glioblastoma. Experimental Design: 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 DNAbinding 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). Conclusion: 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.

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SSBP2 variants are associated with survival in glioblastoma patients

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