Common variation in genes related to innate immunity and risk of adult glioma

Preetha Rajaraman, Alina V Brenner, Mary Ann Butler, Sophia S Wang, Ruth M Pfeiffer, Avima M Ruder, Martha S Linet, Meredith Yeager, Zhaoming Wang, Nick Orr, Howard A Fine, Deukwoo Kwon, Gilles Thomas, Nathaniel Rothman, Peter D Inskip, Stephen J Chanock

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41 Citations (Scopus)

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 r(2) 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.

Original languageEnglish
Pages (from-to)1651-8
Number of pages8
JournalCancer Epidemiology Biomarkers & Prevention
Volume18
Issue number5
DOIs
Publication statusPublished - May 2009

Keywords

  • 5-Lipoxygenase-Activating Proteins
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Carrier Proteins
  • Case-Control Studies
  • Cytoskeletal Proteins
  • Epididymal Secretory Proteins
  • European Continental Ancestry Group
  • Female
  • Genetic Variation
  • Genotype
  • Glioblastoma
  • Glioma
  • Humans
  • Interleukin-1 Receptor-Associated Kinases
  • Logistic Models
  • Lymphocyte Antigen 96
  • Male
  • Membrane Proteins
  • Middle Aged
  • Muscle Proteins
  • NADPH Oxidases
  • NF-kappa B p50 Subunit
  • Neuropeptides
  • Polymorphism, Single Nucleotide
  • Risk
  • STAT1 Transcription Factor
  • Selenoprotein P
  • Serpins
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • United States
  • beta-Defensins
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

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  • Cite this

    Rajaraman, P., Brenner, A. V., Butler, M. A., Wang, S. S., Pfeiffer, R. M., Ruder, A. M., Linet, M. S., Yeager, M., Wang, Z., Orr, N., Fine, H. A., Kwon, D., Thomas, G., Rothman, N., Inskip, P. D., & Chanock, S. J. (2009). Common variation in genes related to innate immunity and risk of adult glioma. Cancer Epidemiology Biomarkers & Prevention, 18(5), 1651-8. https://doi.org/10.1158/1055-9965.EPI-08-1041