Inherited variation in immune genes and pathways and glioblastoma risk

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 w...

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Published in:	Carcinogenesis (New York) Vol. 31; no. 10; pp. 1770 - 1777
Main Authors:	SCHWARTZBAUM, Judith A, YUANYUAN XIAO, HEPWORTH, Sarah J, HOULSTON, Richard S, HOSKING, Fay J, JENKINS, Robert B, KOSEL, Matthew L, MCCOY, Lucie S, MCKINNEY, Patricia A, MUIR, Kenneth, PATOKA, Joe S, PRADOS, Michael, YANHONG LIU, RICE, Terri, ROBERTSON, Lindsay B, SCHOEMAKER, Minouk J, SHETE, Sanjay, SWERDLOW, Anthony J, WIEMELS, JoeL, WIENCKE, John K, PING YANG, WRENSCH, Margaret R, TSAVACHIDIS, Spyros, BERGER, Mitchel S, BONDY, Melissa L, CHANG, Jeffrey S, CHANG, Susan M, DECKER, Paul A, BO DING
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-10-2010
Subjects:	Adult Biological and medical sciences Brain Neoplasms - etiology Brain Neoplasms - genetics Brain Neoplasms - immunology Carcinogenesis, carcinogens and anticarcinogens CD25 antigen Cytokines - genetics Female Genome-Wide Association Study Glioblastoma - etiology Glioblastoma - genetics Glioblastoma - immunology Humans Male Medical sciences Medicin och hälsovetenskap Molecular Epidemiology Neurology Polymorphism, Single Nucleotide Signal Transduction Tumors Tumors of the nervous system. Phacomatoses Malignant glioma Nervous system diseases Gene Central nervous system disease Risk factor Glioblastoma Variations Genetics Malignant tumor Hereditary Cancer
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 These authors contributed equally to this manuscript.
ISSN:	0143-3334 1460-2180 1460-2180
DOI:	10.1093/carcin/bgq152