Levels of Inflammation Markers Are Associated with the Risk of Recurrence and All-Cause Mortality in Patients with Colorectal Cancer
Evertine Wesselink, Michiel G.J. Balvers, Dieuwertje E. Kok, Renate M. Winkels, Moniek van Zutphen, Ruud W.M. Schrauwen, Eric T.P. Keulen, Ewout A. Kouwenhoven, Stéphanie O. Breukink, Renger F. Witkamp, Johannes H.W. de Wilt, Martijn J.L. Bours, Matty P. Weijenberg, Ellen Kampman, Fränzel J.B. van Duijnhoven
Abstract
Abstract Background: We investigated whether preoperative and postoperative levels of inflammation markers, which have mechanistically been linked to colorectal cancer progression, were associated with recurrence and all-cause mortality in patients with colorectal cancer. Methods: Data of two prospective cohort studies were used. For the current analysis, patients with stage I to III colorectal cancer were considered. Data on inflammation [IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and a combined inflammatory z-score] were available for 747 patients before surgery and for 614 patients after surgery. The associations between inflammation marker levels and colorectal cancer recurrence and all-cause mortality were examined using multivariable Cox proportional hazard regression models, considering patient characteristics and clinical and lifestyle factors. Results: Higher preoperative and postoperative hsCRP levels were associated with a higher risk of recurrence [HRper doubling (95% CI), 1.15 (1.02–1.30) and 1.34 (1.16–1.55)] and all-cause mortality [HRper doubling (95% CI) 1.13 (1.01–1.28) and 1.15 (0.98–1.35)]. A doubling in IL8 levels (preoperative levels HR = 1.23; 95% CI, 1.00–1.53 and postoperative levels HR = 1.61; 95% CI, 1.23–2.12) and a higher combined inflammatory z-score (preoperative HRper doubling = 1.39; 95% CI, 1.03–1.89 and postoperative HRper doubling = 1.56; 95% CI, 1.06–2.28) were associated with a higher risk of all-cause mortality, but not recurrence. No associations between IL6, IL10, and TNFα and recurrence or all-cause mortality were observed. Conclusions: Preoperative and postoperative levels of specific inflammation markers were associated with recurrence and/or all-cause mortality. Impact: The complex role of inflammation in cancer recurrence merits further elucidation by investigating local inflammation at the tumor site.