Gastroenterology
Volume 140, Issue 3 , Pages 799-808.e2, March 2011

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

  • Andrew T. Chan

      Affiliations

    • Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    • Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Corresponding Author InformationReprint requests Address requests for reprints to: Andrew T. Chan, MD, MPH, Gastrointestinal Unit, Massachusetts General Hospital GRJ-722, Boston, Massachusetts 02114. fax: (617) 726-3673
    • ,
  • Shuji Ogino

      Affiliations

    • Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
    • ,
  • Edward L. Giovannucci

      Affiliations

    • Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    • Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
    • ,
  • Charles S. Fuchs

      Affiliations

    • Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts

Received 20 April 2010; accepted 8 November 2010. published online 29 November 2010.

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.

Keywords: Colon Cancer, Prevention, Inflammation, Chemoprevention

Abbreviations used in this paper: CI, confidence interval, CRP, C-reactive protein, IL, interleukin, RR, relative risk, sTNFR-2, soluble tumor necrosis factor receptor 2, TNF, tumor necrosis factor

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 This article has an accompanying continuing medical education activity on page e11. Learning Objective: Upon completion of this CME activity, successful learners will be able to assess the importance of inflammation in the pathogenesis of colorectal cancer.

 Conflicts of interest The authors disclose the following: Dr Chan has served as a consultant to Bayer HealthCare. Dr Ogino, Dr Giovannucci, and Dr Fuchs disclose no conflicts.

 Funding Supported by grants R01 137178, U01 CA049449. P01CA87969, P01CA55075, and P50CA127003 from the National Institutes of Health. Dr Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator.

PII: S0016-5085(10)01731-2

doi:10.1053/j.gastro.2010.11.041

Gastroenterology
Volume 140, Issue 3 , Pages 799-808.e2, March 2011

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