Your browser doesn't support javascript.
loading
The immunogenetics of viral antigen response is associated with subtype-specific glioma risk and survival.
Guerra, Geno; Kachuri, Linda; Wendt, George; Hansen, Helen M; Mack, Steven J; Molinaro, Annette M; Rice, Terri; Bracci, Paige; Wiencke, John K; Kasahara, Nori; Eckel-Passow, Jeanette E; Jenkins, Robert B; Wrensch, Margaret; Francis, Stephen S.
Afiliação
  • Guerra G; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. Electronic address: geno.guerra@ucsf.edu.
  • Kachuri L; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
  • Wendt G; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Hansen HM; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Mack SJ; Department of Pediatrics, University of California, San Francisco, Oakland, CA, USA.
  • Molinaro AM; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
  • Rice T; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Bracci P; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
  • Wiencke JK; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; Institute of Human Genetics, University of California, San Francisco, San Francisco, CA,
  • Kasahara N; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, USA.
  • Eckel-Passow JE; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Jenkins RB; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Wrensch M; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Institute of Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
  • Francis SS; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisc
Am J Hum Genet ; 109(6): 1105-1116, 2022 06 02.
Article em En | MEDLINE | ID: mdl-35550063
ABSTRACT
Glioma is a highly fatal cancer with prognostically significant molecular subtypes and few known risk factors. Multiple studies have implicated infections in glioma susceptibility, but evidence remains inconsistent. Genetic variants in the human leukocyte antigen (HLA) region modulate host response to infection and have been linked to glioma risk. In this study, we leveraged genetic predictors of antibody response to 12 viral antigens to investigate the relationship with glioma risk and survival. Genetic reactivity scores (GRSs) for each antigen were derived from genome-wide-significant (p < 5 × 10-8) variants associated with immunoglobulin G antibody response in the UK Biobank cohort. We conducted parallel analyses of glioma risk and survival for each GRS and HLA alleles imputed at two-field resolution by using data from 3,418 glioma-affected individuals subtyped by somatic mutations and 8,156 controls. Genetic reactivity scores to Epstein-Barr virus (EBV) ZEBRA and EBNA antigens and Merkel cell polyomavirus (MCV) VP1 antigen were associated with glioma risk and survival (Bonferroni-corrected p < 0.01). GRSZEBRA and GRSMCV were associated in opposite directions with risk of IDH wild-type gliomas (ORZEBRA = 0.91, p = 0.0099/ORMCV = 1.11, p = 0.0054). GRSEBNA was associated with both increased risk for IDH mutated gliomas (OR = 1.09, p = 0.040) and improved survival (HR = 0.86, p = 0.010). HLA-DQA1∗0301 was significantly associated with decreased risk of glioma overall (OR = 0.85, p = 3.96 × 10-4) after multiple testing adjustment. This systematic investigation of the role of genetic determinants of viral antigen reactivity in glioma risk and survival provides insight into complex immunogenomic mechanisms of glioma pathogenesis. These results may inform applications of antiviral-based therapies in glioma treatment.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Vírus Epstein-Barr / Glioma / Esclerose Múltipla Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Vírus Epstein-Barr / Glioma / Esclerose Múltipla Idioma: En Ano de publicação: 2022 Tipo de documento: Article