@article{fd2225895aca4fdf88110461fab5ccd3,
title = "Inherited variation in immune genes and pathways and glioblastoma risk",
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.",
author = "Schwartzbaum, {Judith A.} and Yuanyuan Xiao and Yanhong Liu and Spyros Tsavachidis and Berger, {Mitchel S.} and Bondy, {Melissa L.} and Chang, {Jeffrey S.} and Chang, {Susan M.} and Decker, {Paul A.} and Bo Ding and Hepworth, {Sarah J.} and Houlston, {Richard S.} and Hosking, {Fay J.} and Jenkins, {Robert B.} and Kosel, {Matthew L.} and McCoy, {Lucie S.} and McKinney, {Patricia A.} and Kenneth Muir and Patoka, {Joe S.} and Michael Prados and Terri Rice and Robertson, {Lindsay B.} and Schoemaker, {Minouk J.} and Sanjay Shete and Swerdlow, {Anthony J.} and Wiemels, {Joe L.} and Wiencke, {John K.} and Ping Yang and Wrensch, {Margaret R.}",
note = "Funding Information: Funding for work at the University of Texas, MDA was provided by US NIH grants 5R01 CA119215 and 5R01 CA070917. Additional support was obtained from the American Brain Tumor Association and the National Brain Tumor Society. Funding Information: Work at UCSF has been supported by National Institutes of Health (NIH) grants R01CA52689 and UCSF Brain Tumor SPORE, P50CA097257, as well as by grants from the National Brain Tumor Foundation, the UCSF Lewis Chair in Brain Tumor Research and by donations from families and friends of John Berardi, Helen Glaser and Elvera Olsen. J.S. was also supported by a fellowship from the National Cancer Institute (grant R25 CA 112355). The UCSF Adult Glioma Study thanks the Northern California Cancer Center for glioma patient case finding; we also thank Kenneth Aldape for pathology review and the pathology departments of Alexian, Alta Bates, Brookside, California Pacific, Doctors Pinole, Eden, El Camino, Good Samaritan, Highland, John Muir, Kaiser Redwood City, Kaiser San Francisco, Kaiser Santa Teresa, Los Gatos, Los Medanos, Marin General, Merrithew, Mills Peninsula, Mt Diablo Hospital, Mt Zion, Naval Hospital, O{\textquoteright}Connor, Ralph K Davies, Saint Louise, San Francisco General, San Jose, San Leandro, San Mateo County, San Ramon Valley, Santa Clara Valley, Sequoia, Seton, St Francis, St Luke{\textquoteright}s, St Rose, Stanford, Summit, UCSF, Valley Livermore, Veterans Palo Alto, Veterans San Francisco and Washington Hospitals and Medical Centers for providing tumor specimens for review. Genotyping services for San Francisco study subjects were provided by deCODE genetics, Iceland (www.decodeservices.com). The company provided SNP and normalized copy number variation data and technical support in data analysis. Thanks to Karl Kelsey, Professor of Community Health and Pathology and Laboratory Medicine, Brown University, for helpful suggestions on genotyping and interpretation of results. Funding Information: The Wellcome Trust provided principal funding for the study. In the UK, additional funding was provided by Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the European Union (CPRB LSHC-CT-2004-503465). The UK and Swedish INTERPHONE studies were supported by the European Union Fifth Framework Program {\textquoteleft}Quality of life and Management of Living Resources{\textquoteright} (contract number QLK4-CT-1999-01563) and the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers{\textquoteright} Forum and Groupe Speciale Mobile Association. Provision of funds via the UICC was governed by agreements that guaranteed INTERPHONE{\textquoteright}s complete scientific independence. These agreements are publicly available at http://www.iarc.fr/ENG/Units/ RCAd.html. The UK Interphone study was also supported by the Mobile Telecommunications and Health Research Program. The Institute of Cancer Research acknowledges funding to the National Institute for Health Research Biomedical Research Centre. The views expressed in this publication are those of the authors and not necessarily those of the funders. Funding Information: Work at the Mayo Clinic was supported by the Mayo Clinic Brain Tumor SPORE (NIH P50 CA108961), the Mayo Clinic Comprehensive Cancer Center (P30 CA15083) and the Bernie and Edith Waterman Foundation. We thank B.Scheithauer and C.Gianinni for their careful histological review of all the primary high-grade gliomas collected at the Mayo Clinic for this study. The Mayo Clinic Comprehensive Cancer Center Biospecimens and Processing (TACMA), Gene Analysis, Biostatistics and Bioinformatics Shared Resources were essential for the success of this study. Funding Information: Dr J.S.{\textquoteright}s work was funded by The Neurosciences Signature Program, College of Medicine, Ohio State University; USA and the National Cancer Institute, R01CA122163.",
year = "2010",
month = jul,
day = "28",
doi = "10.1093/carcin/bgq152",
language = "English (US)",
volume = "31",
pages = "1770--1777",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "10",
}