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Article

Inflammation Is a Mediating Factor in the Association between Lifestyle and Fatigue in Colorectal Cancer Patients

1
Division of Human Nutrition and Health, Wageningen University, Wageningen, 6708 WE, The Netherlands
2
Ziekenhuis Groep Twente, Department of Surgery, Almelo, 7600 SZ, The Netherlands
3
Zuyderland Medical Centre, Department of Gastroenterology, Sittard-Geleen, 6162 BG, The Netherlands
4
Department of Internal Medicine, Admiraal de Ruyter Ziekenhuis, Goes, 4462 RA, The Netherlands
5
Medical Center, Department of Surgery, Maastricht University, Maastricht, 6229 HX, The Netherlands
6
Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, 6200 MD, The Netherlands
7
Medical Centre, Department of Surgery, Radboud University, Nijmegen, 6500 HB, The Netherlands
8
Department of Research & Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, 3511 DT, The Netherlands
*
Author to whom correspondence should be addressed.
Contributed equally.
Cancers 2020, 12(12), 3701; https://doi.org/10.3390/cancers12123701
Received: 23 October 2020 / Revised: 5 December 2020 / Accepted: 7 December 2020 / Published: 9 December 2020
Fatigue is common among colorectal cancer patients. A healthier lifestyle may beneficially affect fatigue, although data are sparse. A healthier lifestyle may result in lower levels of inflammation, which is one of the suggested mechanisms by which lifestyle could influence fatigue. In an observational study, we investigated 1) whether a healthier lifestyle was associated with less fatigue among colorectal cancer patients, and 2) whether this association could be explained by inflammation. We showed that a healthier lifestyle was associated with less fatigue, and that inflammation levels mediated this association. Future intervention studies should investigate whether improving lifestyle after cancer diagnosis results in lowering of inflammation markers and subsequent fatigue.
Fatigue is very common among colorectal cancer (CRC) patients. We examined the association between adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations and fatigue among stage I-III CRC patients, and whether inflammation mediated this association. Data from two prospective cohort studies were used. Adherence to the WCRF/AICR recommendations was expressed as a score ranging from 0–7, and assessed shortly after diagnosis. Six months post-diagnosis, fatigue was assessed with the European Organization for Research and Treatment of Cancer quality of life questionnaire C30 (EORTC QLQ-C30), and in a subpopulation, the plasma levels of inflammation markers (IL6, IL8, TNFα, and hsCRP) were assessed. Multiple linear regression analyses were performed to investigate the association between adherence to the WCRF/AICR recommendations and fatigue. To test mediation by inflammation, the PROCESS analytic tool developed by Hayes was used. A higher WCRF/AICR adherence score was associated with less fatigue six months after diagnosis (n = 1417, β −2.22, 95%CI −3.65; −0.78). In the population of analysis for the mediation analyses (n = 551), the total association between lifestyle and fatigue was (β −2.17, 95% CI −4.60; 0.25). A statistically significant indirect association via inflammation was observed (β −0.97, 95% CI −1.92; −0.21), explaining 45% of the total association between lifestyle and fatigue (−0.97/−2.17 × 100). Thus, inflammation is probably one of the underlying mechanisms linking lifestyle to fatigue. View Full-Text
Keywords: fatigue; colorectal cancer; inflammation markers; lifestyle; mediation analyses fatigue; colorectal cancer; inflammation markers; lifestyle; mediation analyses
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MDPI and ACS Style

Wesselink, E.; van Baar, H.; van Zutphen, M.; Tibosch, M.; Kouwenhoven, E.A.; Keulen, E.T.P.; Kok, D.E.; van Halteren, H.K.; Breukink, S.O.; de Wilt, J.H.W.; Weijenberg, M.P.; Kenkhuis, M.-F.; Balvers, M.G.J.; Witkamp, R.F.; van Duijnhoven, F.J.B.; Kampman, E.; Beijer, S.; Bours, M.J.L.; Winkels, R.M. Inflammation Is a Mediating Factor in the Association between Lifestyle and Fatigue in Colorectal Cancer Patients. Cancers 2020, 12, 3701. https://doi.org/10.3390/cancers12123701

AMA Style

Wesselink E, van Baar H, van Zutphen M, Tibosch M, Kouwenhoven EA, Keulen ETP, Kok DE, van Halteren HK, Breukink SO, de Wilt JHW, Weijenberg MP, Kenkhuis M-F, Balvers MGJ, Witkamp RF, van Duijnhoven FJB, Kampman E, Beijer S, Bours MJL, Winkels RM. Inflammation Is a Mediating Factor in the Association between Lifestyle and Fatigue in Colorectal Cancer Patients. Cancers. 2020; 12(12):3701. https://doi.org/10.3390/cancers12123701

Chicago/Turabian Style

Wesselink, Evertine, Harm van Baar, Moniek van Zutphen, Meilissa Tibosch, Ewout A. Kouwenhoven, Eric T.P. Keulen, Dieuwertje E. Kok, Henk K. van Halteren, Stephanie O. Breukink, Johannes H.W. de Wilt, Matty P. Weijenberg, Marlou-Floor Kenkhuis, Michiel G.J. Balvers, Renger F. Witkamp, Fränzel J.B. van Duijnhoven, Ellen Kampman, Sandra Beijer, Martijn J.L. Bours, and Renate M. Winkels. 2020. "Inflammation Is a Mediating Factor in the Association between Lifestyle and Fatigue in Colorectal Cancer Patients" Cancers 12, no. 12: 3701. https://doi.org/10.3390/cancers12123701

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