Levels of Inflammation Markers Are Associated with the Risk of Recurrence and All-Cause Mortality in Patients with Colorectal Cancer

Cancer Epidemiol Biomarkers Prev. 2021 Jun;30(6):1089-1099. doi: 10.1158/1055-9965.EPI-20-1752. Epub 2021 Mar 26.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / immunology
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / therapy
  • Disease-Free Survival
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / diagnosis
  • Inflammation / immunology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Observational Studies as Topic
  • Prospective Studies
  • Risk Assessment / statistics & numerical data
  • Risk Factors

Substances

  • Biomarkers, Tumor