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breast cancer, cancer survivors, fatigue, fish oil, mitochondria, mitochondrial DNA



  1. Kleckner, Amber S.
  2. Kleckner, Ian R.
  3. Culakova, Eva
  4. Wojtovich, Andrew P.
  5. Klinedinst, N. Jennifer
  6. Kerns, Sarah L.
  7. Hardy, Sara J.
  8. Inglis, Julia E.
  9. Padula, Gilbert D. A.
  10. Mustian, Karen M.
  11. Janelsins, Michelle C.
  12. Dorsey, Susan G.
  13. Saligan, Leorey N.
  14. Peppone, Luke J.


Background: Cancer-related fatigue is a prevalent, debilitating, and persistent condition. Mitochondrial dysfunction is a putative contributor to cancer-related fatigue, but relationships between mitochondrial function and cancer-related fatigue are not well understood.


Objectives: We investigated the relationships between mitochondrial DNA (mtDNA) gene expression and cancer-related fatigue, as well as the effects of fish and soybean oil supplementation on these relationships.


Methods: A secondary analysis was performed on data from a randomized controlled trial of breast cancer survivors 4-36 months posttreatment with moderate-severe cancer-related fatigue. Participants were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g each daily for 6 weeks. At pre- and postintervention, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and provided whole blood for assessment of mtDNA gene expression. The expression of 12 protein-encoding genes was reduced to a single dimension using principal component analysis for use in regression analysis. Relationships between mtDNA expression and cancer-related fatigue were assessed using linear regression.


Results: Among 68 participants, cancer-related fatigue improved and expression of all mtDNA genes decreased over 6 weeks with no effect of treatment group on either outcome. Participants with lower baseline mtDNA gene expression had greater improvements in cancer-related fatigue. No significant associations were observed between mtDNA gene expression and cancer-related fatigue at baseline or changes in mtDNA gene expression and changes in cancer-related fatigue.


Discussion: Data from this exploratory study add to the growing literature that mitochondrial dysfunction may contribute to the etiology and pathophysiology of cancer-related fatigue.