Publications

Levels of inflammation markers are associated with the risk of recurrence and all-cause mortality in patients with colorectal cancer

Wesselink, Evertine; Balvers, Michiel G.J.; Kok, Dieuwertje E.; Winkels, Renate M.; van Zutphen, Moniek; Schrauwen, Ruud W.M.; Keulen, Eric T.P.; Kouwenhoven, Ewout A.; Breukink, Stephanie O.; Witkamp, Renger F.; de Wilt, Johannes H.W.; Bours, Martijn J.L.; Weijenberg, Matty P.; Kampman, Ellen; van Duijnhoven, Fränzel J.B.

Summary

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, TNFa, 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 [HR_per doubling (95% CI), 1.15 (1.02-1.30) and 1.34 (1.16-1.55)] and all-cause mortality [HR_{per doubling} (95% CI) 1.13 (1.01-1.28) and 1.15 (0.98-1.35)]. A doubling in IL8 levels (preoperative levels HR ¼ 1.23; 95% CI, 1.00-1.53 and postoperative levels HR ¼ 1.61; 95% CI, 1.23-2.12) and a higher combined inflammatory z-score (preoperative HR_{per doubling} ¼ 1.39; 95% CI, 1.03-1.89 and postoperative HR_{per doubling} ¼ 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 TNFa 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.