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

Simple Summary 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, TNF alpha, 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, beta -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 (beta -2.17, 95% CI -4.60; 0.25). A statistically significant indirect association via inflammation was observed (beta -0.97, 95% CI -1.92; -0.21), explaining 45% of the total association between lifestyle and fatigue (-0.97/-2.17 x 100). Thus, inflammation is probably one of the underlying mechanisms linking lifestyle to fatigue.