Genomic mechanisms of fatigue in colorectal cancer survivors

Details

• Alternative Title:
  Cancer
• Personal Author:
  Black, David S. ; Cole, Steve ; Christodoulou, Georgia ; Figueiredo, Jane C.
• Description:
  Objective
  
  Many cancer survivors experience fatigue as a nagging symptom lasting years after treatment. To learn of the relevant biological pathways involved in fatigue among cancer survivors, we tested for an association between fatigue levels and leukocyte gene expression profiles and determined the specific mediating immune cell types.
  
  Methods
  
  A sample of N=89 Hispanic/Latino adults diagnosed with colorectal cancer aged 60.5 years, 2.9 years since diagnosis, and 62% male provided blood for transcriptome profiling and completed a validated measure of fatigue (Multidimensional Fatigue Inventory-Short Form). We applied genome-wide transcriptional profiling of leukocyte RNA to identify gene expression activity associated with fatigue, tested for activity of specific transcription factors involved in previously established markers of inflammation and immunologic activation, and identified the specific cell types mediating these transcriptional alterations.
  
  Results
  
  In analyses adjusting for demographic and behavioral health risk factors, results linked fatigue to increased activation of B lymphocytes and CD8+ T cells, as well as several transcription factors involved in immune activation (NF-κB, STAT, and CREB). Results also replicated several specific genomic effects previously observed in fatigued cancer survivors, including up-regulated expression of alpha-synuclein (SNCA) and hemoglobin subunits (HBA and HBB).
  
  Conclusions
  
  Cancer survivors’ heightened fatigue levels may be partially explained by activation of specific immune cell subsets, providing a potential molecular biomarker for clinical interventions targeting the remediation of fatigue.
  
  
• Subjects:
  Article Cancer Colorectal Fatigue Genomics Hispanic Inflammation Leukocyte Oncology Survivorship Transcriptome

  More +
• Source:
  Cancer. 124(12):2637-2644
• Pubmed ID:
  29579369
• Pubmed Central ID:
  PMC5990448
• Document Type:
  Journal Article
• Funding:
  L30 AT008380/AT/NCCIH NIH HHS/United States ; HHSN261201000140C/CA/NCI NIH HHS/United States ; HHSN261201000035C/CA/NCI NIH HHS/United States ; R01 CA155101/CA/NCI NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; P30 AI028697/AI/NIAID NIH HHS/United States ; HHSN261201000035I/CA/NCI NIH HHS/United States ; HHSN261201000034C/CA/NCI NIH HHS/United States ; P30 AG017265/AG/NIA NIH HHS/United States ; U58 DP003862/DP/NCCDPHP CDC HHS/United States
• Volume:
  124
• Issue:
  12
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d6374d56842fe783097ff32b610f91115385a5ff49a2ecb0a289c1f40f9aa0f2
• Download URL:
  https://stacks.cdc.gov/view/cdc/55678/cdc_55678_DS1.pdf
• File Type:
  [PDF - 480.37 KB ]