Genetic Epidemiology of Glioblastoma Multiforme: Confirmatory and New Findings from Analyses of Human Leukocyte Antigen Alleles and Motifs

Details

• Personal Author:
  Butler M ; Hu L ; Kaslow RA ; Li Y ; Ni R ; Ruder, Avima M. ; Shao W ; Song W ; Tang J
• Description:
  Background: Human leukocyte antigen (HLA) class I genes mediate cytotoxic T-lymphocyte responses and natural killer cell function. In a previous study, several HLA-B and HLA-C alleles and haplotypes were positively or negatively associated with the occurrence and prognosis of glioblastoma multiforme (GBM). Methodology/Principal Findings: As an extension of the Upper Midwest Health Study, we have performed HLA genotyping for 149 GBM patients and 149 healthy control subjects from a non-metropolitan population consisting almost exclusively of European Americans. Conditional logistic regression models did not reproduce the association of HLA-B*07 or the B*07-Cw*07 haplotype with GBM. Nonetheless, HLA-A*32, which has previously been shown to predispose GBM patients to a favorable prognosis, was negatively associated with occurrence of GBM (odds ratio = 0.41, p = 0.04 by univariate analysis). Other alleles (A*29, A*30, A*31 and A*33) within the A19 serology group to which A*32 belongs showed inconsistent trends. Sequencingbased HLA-A genotyping established that A*3201 was the single A*32 allele underlying the observed association. Additional evaluation of HLA-A promoter and exon 1 sequences did not detect any unexpected single nucleotide polymorphisms that could suggest differential allelic expression. Further analyses restricted to female GBM cases and controls revealed a second association with a specific HLA-B sequence motif corresponding to Bw4-80Ile (odds ratio = 2.71, p = 0.02). Conclusions/Significance: HLA-A allelic product encoded by A*3201 is likely to be functionally important to GBM. The novel, sex-specific association will require further confirmation in other representative study populations. [Description provided by NIOSH]
• Subjects:
  Antigens Genetics Occupational Health Safety Sex Characteristics
• Keywords:
  Biological-effects Cell-biology Cell-function Cellular-function Cellular-reactions Genes Genetic-factors Hepatocytes Human-factors-engineering Humans Liver-cells Sex-factors

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• ISSN:
  1932-6203
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DSHEFS - Division of Surveillance, Hazard Evaluations, and Field Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  4
• Issue:
  9
• NIOSHTIC Number:
  nn:20036105
• Citation:
  PLoS One 2009 Sep; 4(9):e7157
• Contact Point Address:
  Jianming Tang, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
• Email:
  jtang@uab.edu
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Peer Reviewed:
  True
• Source Full Name:
  PLoS One
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1fa663c33d9b68ed183cc54956d957378d182ad332c8652fb0e181e60a2b5552273ff80b82e12cc94713413ac9c3f07e8192b0b5466f542724c1aca229fe0e15
• Download URL:
  https://stacks.cdc.gov/view/cdc/187684/cdc_187684_DS1.pdf
• File Type:
  [PDF - 349.76 KB ]