Journal Article

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 B. Jenkins, Matthew L. Kosel, Lucie S. McCoy, Patricia A. McKinney, Kenneth Muir, Joe S. Patoka, Michael Prados, Terri Rice, Lindsay B. Robertson, Minouk J. Schoemaker, Sanjay Shete, Anthony J. Swerdlow, Joe L. Wiemels, John K. Wiencke, Ping Yang and Margaret R. Wrensch

in Carcinogenesis

Volume 31, issue 10, pages 1770-1777
Published in print October 2010 | ISSN: 0143-3334
Published online July 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq152

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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.

Journal Article.  6819 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.