Common Variation in Genes Related to Innate Immunity and Risk of Adult Glioma
- Preetha Rajaraman1,
- Alina V. Brenner1,
- Mary Ann Butler3,
- Sophia S. Wang1,
- Ruth M. Pfeiffer1,
- Avima M. Ruder3,
- Martha S. Linet1,
- Meredith Yeager4,
- Zhaoming Wang4,
- Nick Orr4,
- Howard A. Fine2,
- Deukwoo Kwon1,
- Gilles Thomas4,
- Nathaniel Rothman1,
- Peter D. Inskip1 and
- Stephen J. Chanock4
- 1Division of Cancer Epidemiology and Genetics and 2Neuro-oncology Branch, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; 3National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Department of Health and Human Services, Cincinnati, Ohio; and 4Core Genotyping Facility, Advanced Technology Program, SAIC Frederick, Inc, NCI-Frederick, Frederick, Maryland
- Requests for reprints:
Preetha Rajaraman, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS Room 7058, Rockville, MD 20852. Phone: 301-496-8847; Fax: 301-402-0207. E-mail: rajarama{at}mail.nih.gov
Abstract
Current evidence suggests that immune system alterations contribute to the etiology of adult glioma, the most common adult brain tumor. Although previous studies have focused on variation in candidate genes in the adaptive immune system, the innate immune system has emerged as a critical avenue for research given its known link with carcinogenesis. To identify genetic markers in pathways critical to innate immunity, we conducted an association study of 551 glioma cases and 865 matched controls of European ancestry to investigate “tag” single nucleotide polymorphisms (SNP) in 148 genetic regions. Two independent U.S. case-control studies included were as follows: a hospital-based study conducted by the National Cancer Institute (263 cases, 330 controls) and a community-based study conducted by the National Institute for Occupational Safety and Health (288 cases, 535 controls). Tag SNPs (1,397) chosen on the basis of an r2 of >0.8 and minor allele frequency of >5% in Caucasians in HapMap1 were genotyped. Glioma risk was estimated by odds ratios. Nine SNPs distributed across eight genetic regions (ALOX5, IRAK3, ITGB2, NCF2, NFKB1, SELP, SOD1, and STAT1) were associated with risk of glioma with P value of <0.01. Although these associations were no longer statistically significant after controlling for multiple comparisons, the associations were notably consistent in both studies. Region-based tests were statistically significant (P < 0.05) for SELP, SOD, and ALOX5. Analyses restricted to glioblastoma (n = 254) yielded significant associations for the SELP, DEFB126/127, SERPINI1, and LY96 genetic regions. We have identified a promising set of innate immunity-related genetic regions for further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1651–8)
Footnotes
-
↵5 http://tagzilla.nci.nih.gov/ last accessed 22 December 2008.
-
Grant support: Intramural funds from the NCI, NIH, Department of Health and Human Services, and has been funded in whole or in part with federal funds from the NCI, NIH, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
-
Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).
-
P. Rajaraman and A.V. Brenner contributed equally to this work.
-
- Accepted March 3, 2009.
- Received November 3, 2008.
- Revision received December 23, 2008.
