Inflammatory Markers Are Associated With Risk of Colorectal Cancer and Chemopreventive Response to Anti-Inflammatory Drugs

Gastroenterology. 2011 Mar;140(3):799-808, quiz e11. doi: 10.1053/j.gastro.2010.11.041. Epub 2010 Nov 27.

Abstract

Background & aims: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) lower the risk of colorectal cancer (CRC). We investigated whether plasma inflammatory markers were associated with risk of CRC and if use of anti-inflammatory drugs was differentially associated with risk of CRC according to levels of inflammatory markers.

Methods: We measured levels of high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, and the soluble tumor necrosis factor receptor 2 (sTNFR-2) in blood samples from 32,826 women, collected from 1989 to 1990. Through 2004, we documented 280 cases of incident CRC; each case was matched for age to 2 randomly selected participants without cancer (controls). Information on anti-inflammatory drug (aspirin and NSAIDs) use was collected biennially.

Results: Compared with women in the lowest quartile of plasma levels of sTNFR-2, women in the highest quartile had an increased risk of CRC (multivariate relative risk [RR], 1.67; 95% confidence interval [CI], 1.05-2.68; P for trend = .03). Among women with high baseline levels of sTNFR-2, those who initiated aspirin/NSAID use after blood collection had significant reductions in subsequent risk of CRC (multivariate RR, 0.39; 95% CI, 0.18-0.86). In contrast, among women with low baseline levels of sTNFR-2, initiation of aspirin/NSAID use was not associated with significant risk reduction (multivariate RR, 0.86; 95% CI, 0.41-1.79). Plasma levels of CRP and IL-6 were not significantly associated with CRC risk.

Conclusions: Plasma levels of sTNFR-2, but not CRP or IL-6, are associated with an increased risk of CRC. Anti-inflammatory drugs appear to reduce risk of CRC among women with high, but not low, baseline levels of sTNFR-2. Certain subsets of the population, defined by inflammatory markers, may obtain different benefits from anti-inflammatory drugs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Anticarcinogenic Agents / therapeutic use*
  • Aspirin / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Chi-Square Distribution
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / prevention & control*
  • Female
  • Health Surveys
  • Humans
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood
  • Logistic Models
  • Middle Aged
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor, Type II / blood
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • United States / epidemiology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Biomarkers
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Receptors, Tumor Necrosis Factor, Type II
  • C-Reactive Protein
  • Aspirin