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

Abstract

Background: We investigated whether pre-operative and post-operative levels of inflammation markers, which have mechanistically been linked to colorectal cancer (CRC) progression, were associated with recurrence and all-cause mortality in CRC patients. Methods: Methods: Data of two prospective cohort studies were used. For the current analysis, patients with stage I-III CRC were considered. Data on inflammation (Interleukin (IL)6, IL8, IL10, Tumour Necrosis Factor (TNF)α, high sensitivity C-reactive protein (hsCRP) and a combined inflammatory z-score) was available for 747 patients before surgery and for 614 patients after surgery. The associations between inflammation marker levels and CRC recurrence and all-cause mortality were examined using multivariable Cox proportional hazard regression models, taking into account patient characteristics, clinical- and lifestyle factors. Results: Higher pre-operative as well as post-operative 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 (pre-operative levels HR 1.23 95%CI 1.00-1.53 and post-operative levels HR 1.61 95%CI 1.23-2.12) and a higher combined inflammatory z-score (pre-operative HRper doubling 1.39 95%CI 1.03-1.89 and post-operative 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: Pre-operative and post-operative 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 tumour-site.