Quality of Life Research

, Volume 19, Issue 10, pp 1419–1427

I’m so tired: biological and genetic mechanisms of cancer-related fatigue

  • Andrea Barsevick
  • Marlene Frost
  • Aeilko Zwinderman
  • Per Hall
  • Michele Halyard
  • GENEQOL Consortium

DOI: 10.1007/s11136-010-9757-7

Cite this article as:
Barsevick, A., Frost, M., Zwinderman, A. et al. Qual Life Res (2010) 19: 1419. doi:10.1007/s11136-010-9757-7



The goal of this paper is to discuss cancer-related fatigue (CRF) and address issues related to the investigation into potential biological and genetic causal mechanisms. The objectives are to: (1) describe CRF as a component of quality of life (QOL); (2) address measurement issues that have slowed progress toward an understanding of mechanisms underlying this symptom; (3) review biological pathways and genetic approaches that have promise for the exploration of causal mechanisms of CRF; and (4) offer directions for future research.


Review, synthesis, and interpretation of the literature.


Until recently, CRF and QOL have been understood primarily as subjective patient-reported experiences. With increased understanding of human genetics, theories and research are being expanded to incorporate biological and genetic understandings of these subjective experiences. Proposed biological and genetic mechanisms of CRF that have been examined include cytokine dysregulation, hypothalamic–pituitary–adrenal (HPA) axis dysfunction, five hydroxy tryptophan (5-HT) neurotransmitter dysregulation, circadian rhythm disruption, alterations in adenosine triphosphate (ATP) and muscle metabolism, and vagal afferent activation. Approaches to the study of genetic mechanisms have also been addressed including candidate genes, genome-wide scanning, and gene expression. Based on the review and synthesis of the literature, directions for future research are proposed.


Understanding the biological and genetic basis of CRF has the potential to contribute to a more complete understanding of the genetic determinants of QOL.


Cancer-related fatigue Patient-reported outcomes Biological mechanisms Genetic variables Quality of life 

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Andrea Barsevick
    • 1
  • Marlene Frost
    • 2
  • Aeilko Zwinderman
    • 3
  • Per Hall
    • 4
  • Michele Halyard
    • 5
  • GENEQOL Consortium
  1. 1.Cancer Prevention and Control ProgramFox Chase Cancer CenterPhiladelphiaUSA
  2. 2.Womens’ Cancer ProgramMayo ClinicRochesterUSA
  3. 3.Department of Clinical Epidemiology and BiostatisticsUniversity of AmsterdamAmsterdamThe Netherlands
  4. 4.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  5. 5.Department of Radiation OncologyMayo ClinicScottsdaleUSA

Personalised recommendations