Inherited variation in immune genes and pathways and glioblastoma risk

Judith A. Schwartzbaum, Yuanyuan Xiao, Yanhong Liu, Spyros Tsavachidis, Mitchel S. Berger, Melissa L. Bondy, Jeffrey S. Chang, Susan M. Chang, Paul A. Decker, Bo Ding, Sarah J. Hepworth, Richard S. Houlston, Fay J. Hosking, Robert Brian Jenkins, Matthew L. Kosel, Lucie S. McCoy, Patricia A. McKinney, Kenneth Muir, Joe S. Patoka, Michael PradosTerri Rice, Lindsay B. Robertson, Minouk J. Schoemaker, Sanjay Shete, Anthony J. Swerdlow, Joe L. Wiemels, John K. Wiencke, Ping Yang, Margaret R. Wrensch

Research output: Contribution to journalArticle

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Abstract

To determine whether inherited variations in immune function single-nucleotide polymorphisms (SNPs), genes or pathways affect glioblastoma risk, we analyzed data from recent genome-wide association studies in conjunction with predefined immune function genes and pathways. Gene and pathway analyses were conducted on two independent data sets using 6629 SNPs in 911 genes on 17 immune pathways from 525 glioblastoma cases and 602 controls from the University of California, San Francisco (UCSF) and a subset of 6029 SNPs in 893 genes from 531 cases and 1782 controls from MD Anderson (MDA). To further assess consistency of SNP-level associations, we also compared data from the UK (266 cases and 2482 controls) and the Mayo Clinic (114 cases and 111 controls). Although three correlated epidermal growth factor receptor (EGFR) SNPs were consistently associated with glioblastoma in all four data sets (Mantel-Haenzel P values = 1 × 10-5 to 4 × 10-3), independent replication is required as genome-wide significance was not attained. In gene-level analyses, eight immune function genes were significantly (minP < 0.05) associated with glioblastoma; the IL-2RA (CD25) cytokine gene had the smallest minP values in both UCSF (minP = 0.01) and MDA (minP = 0.001) data sets. The IL-2RA receptor is found on the surface of regulatory T cells potentially contributing to immunosuppression characteristic of the glioblastoma microenvironment. In pathway correlation analyses, cytokine signaling and adhesion-extravasation-migration pathways showed similar associations with glioblastoma risk in both MDA and UCSF data sets. Our findings represent the first systematic description of immune genes and pathways that characterize glioblastoma risk.

Original languageEnglish (US)
Pages (from-to)1770-1777
Number of pages8
JournalCarcinogenesis
Volume31
Issue number10
DOIs
StatePublished - Jul 28 2010

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Glioblastoma
Single Nucleotide Polymorphism
Genes
San Francisco
Cytokines
Genome-Wide Association Study
Regulatory T-Lymphocytes
Epidermal Growth Factor Receptor
Immunosuppression
Genome
Datasets

ASJC Scopus subject areas

  • Cancer Research

Cite this

Schwartzbaum, J. A., Xiao, Y., Liu, Y., Tsavachidis, S., Berger, M. S., Bondy, M. L., ... Wrensch, M. R. (2010). Inherited variation in immune genes and pathways and glioblastoma risk. Carcinogenesis, 31(10), 1770-1777. https://doi.org/10.1093/carcin/bgq152

Inherited variation in immune genes and pathways and glioblastoma risk. / Schwartzbaum, Judith A.; Xiao, Yuanyuan; Liu, Yanhong; Tsavachidis, Spyros; Berger, Mitchel S.; Bondy, Melissa L.; Chang, Jeffrey S.; Chang, Susan M.; Decker, Paul A.; Ding, Bo; Hepworth, Sarah J.; Houlston, Richard S.; Hosking, Fay J.; Jenkins, Robert Brian; Kosel, Matthew L.; McCoy, Lucie S.; McKinney, Patricia A.; Muir, Kenneth; Patoka, Joe S.; Prados, Michael; Rice, Terri; Robertson, Lindsay B.; Schoemaker, Minouk J.; Shete, Sanjay; Swerdlow, Anthony J.; Wiemels, Joe L.; Wiencke, John K.; Yang, Ping; Wrensch, Margaret R.

In: Carcinogenesis, Vol. 31, No. 10, 28.07.2010, p. 1770-1777.

Research output: Contribution to journalArticle

Schwartzbaum, JA, Xiao, Y, Liu, Y, Tsavachidis, S, Berger, MS, Bondy, ML, Chang, JS, Chang, SM, Decker, PA, Ding, B, Hepworth, SJ, Houlston, RS, Hosking, FJ, Jenkins, RB, Kosel, ML, McCoy, LS, McKinney, PA, Muir, K, Patoka, JS, Prados, M, Rice, T, Robertson, LB, Schoemaker, MJ, Shete, S, Swerdlow, AJ, Wiemels, JL, Wiencke, JK, Yang, P & Wrensch, MR 2010, 'Inherited variation in immune genes and pathways and glioblastoma risk', Carcinogenesis, vol. 31, no. 10, pp. 1770-1777. https://doi.org/10.1093/carcin/bgq152
Schwartzbaum JA, Xiao Y, Liu Y, Tsavachidis S, Berger MS, Bondy ML et al. Inherited variation in immune genes and pathways and glioblastoma risk. Carcinogenesis. 2010 Jul 28;31(10):1770-1777. https://doi.org/10.1093/carcin/bgq152
Schwartzbaum, Judith A. ; Xiao, Yuanyuan ; Liu, Yanhong ; Tsavachidis, Spyros ; Berger, Mitchel S. ; Bondy, Melissa L. ; Chang, Jeffrey S. ; Chang, Susan M. ; Decker, Paul A. ; Ding, Bo ; Hepworth, Sarah J. ; Houlston, Richard S. ; Hosking, Fay J. ; Jenkins, Robert Brian ; Kosel, Matthew L. ; McCoy, Lucie S. ; McKinney, Patricia A. ; Muir, Kenneth ; Patoka, Joe S. ; Prados, Michael ; Rice, Terri ; Robertson, Lindsay B. ; Schoemaker, Minouk J. ; Shete, Sanjay ; Swerdlow, Anthony J. ; Wiemels, Joe L. ; Wiencke, John K. ; Yang, Ping ; Wrensch, Margaret R. / Inherited variation in immune genes and pathways and glioblastoma risk. In: Carcinogenesis. 2010 ; Vol. 31, No. 10. pp. 1770-1777.
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AU - Xiao, Yuanyuan

AU - Liu, Yanhong

AU - Tsavachidis, Spyros

AU - Berger, Mitchel S.

AU - Bondy, Melissa L.

AU - Chang, Jeffrey S.

AU - Chang, Susan M.

AU - Decker, Paul A.

AU - Ding, Bo

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AU - Houlston, Richard S.

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