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Genomic mechanisms of fatigue in survivors of colorectal cancer.
- Source :
-
Cancer [Cancer] 2018 Jun 15; Vol. 124 (12), pp. 2637-2644. Date of Electronic Publication: 2018 Mar 26. - Publication Year :
- 2018
-
Abstract
- Background: 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, the authors tested for an association between fatigue levels and leukocyte gene expression profiles and determined the specific mediating immune cell types.<br />Methods: A sample of 89 Hispanic/Latino adults aged 60.5 years, 62% of whom were male, who were diagnosed with colorectal cancer and were 2.9 years since diagnosis provided blood for transcriptome profiling and completed a validated measure of fatigue (Multidimensional Fatigue Symptom Inventory-Short Form). The authors applied genome-wide transcriptional profiling of leukocyte RNA to identify gene expression activity associated with fatigue, tested for the 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.<br />Results: In analyses adjusting for demographic and behavioral health risk factors, results linked fatigue with increased activation of B lymphocytes and CD8-positive T cells, as well as several transcription factors involved in immune activation (nuclear factor κB [NF-κB], signal transducer and activator of transcription [STAT], and cAMP responsive element-binding protein [CREB]). Results also replicated several specific genomic effects previously observed in fatigued cancer survivors, including upregulated expression of α-synuclein (SNCA) and hemoglobin subunits (HBA and HBB).<br />Conclusions: Cancer survivors' heightened fatigue levels may be partially explained by activation of specific immune cell subsets, thereby providing a potential molecular biomarker for clinical interventions targeting the remediation of fatigue. Cancer 2018;124:2637-44. © 2018 American Cancer Society.<br /> (© 2018 American Cancer Society.)
- Subjects :
- Aged
B-Lymphocytes immunology
B-Lymphocytes metabolism
Biomarkers blood
Biomarkers metabolism
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Cohort Studies
Colorectal Neoplasms blood
Colorectal Neoplasms genetics
Colorectal Neoplasms immunology
Computational Biology
Cross-Sectional Studies
Fatigue blood
Fatigue diagnosis
Fatigue genetics
Female
Gene Expression Profiling
Hispanic or Latino genetics
Humans
Inflammation blood
Inflammation genetics
Male
Middle Aged
Self Report
Signal Transduction genetics
Signal Transduction immunology
Cancer Survivors
Colorectal Neoplasms complications
Fatigue immunology
Inflammation immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0142
- Volume :
- 124
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 29579369
- Full Text :
- https://doi.org/10.1002/cncr.31356