Cancer Causes & Control

, Volume 25, Issue 4, pp 409–418 | Cite as

The association between circulating high-sensitivity C-reactive protein concentration and pathologic measures of colonic inflammation

  • Corinne E. Joshu
  • Kostantinos K. Tsilidis
  • Sarah B. Peskoe
  • Francis M. Giardiello
  • Paul J. Dluzniewski
  • William G. Nelson
  • Christine A. Iacobuzio-Donahue
  • Elizabeth A. Platz
Original paper

Abstract

Purpose

C-reactive protein (CRP), an inflammation marker, is associated with colorectal cancer (CRC) risk in some prospective studies. Whether increased CRP is indicative of colonic inflammation, a possible CRC cause, or of other sources of inflammation (e.g., adiposity), is unknown. Thus, we evaluated the association between CRP and colonic mucosal measures of inflammation.

Methods

151 adults undergoing colonoscopy provided a blood sample and random left- and right-side colonic mucosal biopsies. Height and weight were measured, and lifestyle information was collected. High-sensitivity C-reactive protein (hsCRP) was measured by immunoturbidometric assay. A gastrointestinal pathologist evaluated biopsies for seven colonic inflammation measures. Of 119 participants with complete information, 24 had an inflammatory bowel disease (IBD) history and were analyzed separately. We calculated the number of colonic inflammation measures present in both biopsies, and separately for right and left biopsies. Adjusted geometric mean hsCRP was calculated using linear regression, overall, by demographic and lifestyle factors, and inflammation measures.

Results

Most participants had ≥1 colonic inflammation measure (0: 21 %, 1: 39 %, ≥2: 40 %). Adjusted mean hsCRP did not increase with increasing number of inflammation measures (0: 1.67; 1: 1.33; ≥2: 1.01 mg/L; p trend = 0.21). Obese (2.03 mg/L) and overweight (1.61 mg/L) participants had higher adjusted mean hsCRP than normal-weight participants (0.62 mg/L; p trend <0.0001). Patterns were similar for participants with a history of IBD.

Conclusions

hsCRP concentration was not associated with colonic inflammation, although hsCRP increased with adiposity. The hsCRP–CRC association may be explained by residual confounding by other risk factors, such as adiposity, rather than by CRP marking colonic inflammation.

Keywords

C-reactive protein Inflammation Colorectal cancer Obesity 

Notes

Acknowledgments

This study was supported by Seraph Foundation; Frederik B. Bang Award for Student Research in Pathobiology, Johns Hopkins Bloomberg School of Public Health; Maryland Cigarette Restitution Fund at Johns Hopkins; and the National Cancer Institute (T32 CA009314). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Conflict of interest

The authors have no conflict of interest to disclose.

References

  1. 1.
    Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48:526–535PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Herszenyi L, Miheller P, Tulassay Z (2007) Carcinogenesis in inflammatory bowel disease. Dig Dis 25:267–269PubMedCrossRefGoogle Scholar
  3. 3.
    Dube C, Rostom A, Lewin G et al (2007) The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 146:365–375PubMedCrossRefGoogle Scholar
  4. 4.
    Rothwell PM, Wilson M, Elwin CE et al (2010) Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376:1741–1750PubMedCrossRefGoogle Scholar
  5. 5.
    Tsilidis KK, Branchini C, Guallar E, Helzlsouer KJ, Erlinger TP, Platz EA (2008) C-reactive protein and colorectal cancer risk: a systematic review of prospective studies. Int J Cancer 123:1133–1140PubMedCrossRefGoogle Scholar
  6. 6.
    Aleksandrova K, Jenab M, Boeing H et al (2010) Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case–control study within the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol 172:407–418PubMedCrossRefGoogle Scholar
  7. 7.
    Prizment AE, Anderson KE, Visvanathan K, Folsom AR (2011) Association of inflammatory markers with colorectal cancer incidence in the atherosclerosis risk in communities study. Cancer Epidemiol Biomark Prev 20:297–307CrossRefGoogle Scholar
  8. 8.
    Allin KH, Bojesen SE, Nordestgaard BG (2009) Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 27:2217–2224PubMedCrossRefGoogle Scholar
  9. 9.
    Heikkila K, Harris R, Lowe G et al (2009) Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis. Cancer Causes Control 20:15–26PubMedCrossRefGoogle Scholar
  10. 10.
    Allin KH, Nordestgaard BG, Zacho J, Tybjaerg-Hansen A, Bojesen SE (2010) C-reactive protein and the risk of cancer: a Mendelian randomization study. J Natl Cancer Inst 102:202–206PubMedCrossRefGoogle Scholar
  11. 11.
    Chan AT, Ogino S, Giovannucci EL, Fuchs CS (2011) Inflammatory markers are associated with risk of colorectal cancer and chemopreventive response to anti-inflammatory drugs. Gastroenterology 140:799–808 (quiz e11)PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    World Cancer Research Fund/American Institute for Cancer Research (2011) Continuous update project. Food, nutrition, physical activity, and the prevention of colorectal cancer. AICR, Washington, DCGoogle Scholar
  13. 13.
    Cerilli LA, Greenson JK (2012) The differential diagnosis of colitis in endoscopic biopsy specimens: a review article. Arch Pathol Lab Med 136:854–864PubMedCrossRefGoogle Scholar
  14. 14.
    Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB (1999) Elevated C-reactive protein levels in overweight and obese adults. JAMA 282:2131–2135PubMedCrossRefGoogle Scholar
  15. 15.
    Wee CC, Mukamal KJ, Huang A, Davis RB, McCarthy EP, Mittleman MA (2008) Obesity and C-reactive protein levels among white, black, and Hispanic US adults. Obesity (Silver Spring) 16:875–880CrossRefGoogle Scholar
  16. 16.
    Poullis A, Foster R, Shetty A, Fagerhol MK, Mendall MA (2004) Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk. Cancer Epidemiol Biomark Prev 13:279–284CrossRefGoogle Scholar
  17. 17.
    Vermeire S, Van Assche G, Rutgeerts P (2006) Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut 55:426–431PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Henriksen M, Jahnsen J, Lygren I et al (2008) C-reactive protein: a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based study. Gut 57:1518–1523PubMedCrossRefGoogle Scholar
  19. 19.
    Solem CA, Loftus EV Jr, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ (2005) Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis 11:707–712PubMedCrossRefGoogle Scholar
  20. 20.
    Sabatine MS, Morrow DA, Jablonski KA et al (2007) Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation 115:1528–1536PubMedCrossRefGoogle Scholar
  21. 21.
    Rifai N, Ridker PM (2003) Population distributions of C-reactive protein in apparently healthy men and women in the United States: implication for clinical interpretation. Clin Chem 49:666–669PubMedCrossRefGoogle Scholar
  22. 22.
    Ullman TA, Itzkowitz SH (2011) Intestinal inflammation and cancer. Gastroenterology 140:1807–1816PubMedCrossRefGoogle Scholar
  23. 23.
    Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M (2009) The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer 125:171–180PubMedCrossRefGoogle Scholar
  24. 24.
    World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, Washington, DCGoogle Scholar
  25. 25.
    Fransson EI, Batty GD, Tabak AG et al (2010) Association between change in body composition and change in inflammatory markers: an 11-year follow-up in the Whitehall II Study. J Clin Endocrinol Metab 95:5370–5374PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Hudgins LC, Parker TS, Levine DM et al (2003) A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers. J Lipid Res 44:1489–1498PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Corinne E. Joshu
    • 1
  • Kostantinos K. Tsilidis
    • 2
  • Sarah B. Peskoe
    • 1
  • Francis M. Giardiello
    • 3
    • 4
  • Paul J. Dluzniewski
    • 1
  • William G. Nelson
    • 4
    • 5
    • 6
  • Christine A. Iacobuzio-Donahue
    • 7
  • Elizabeth A. Platz
    • 1
    • 4
    • 6
  1. 1.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  2. 2.Department of Hygiene and Epidemiology, School of MedicineUniversity of IoanninaIoanninaGreece
  3. 3.Division of Gastroenterology, Department of MedicineJohns Hopkins UniversityBaltimoreUSA
  4. 4.Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins Medical InstitutionsBaltimoreUSA
  5. 5.Departments of Oncology, Pathology, Pharmacology and Molecular Sciences, Radiation Oncology and Molecular Radiation SciencesJohns Hopkins Medical InstitutionsBaltimoreUSA
  6. 6.James Buchanan Brady Urological InstituteJohns Hopkins Medical InstitutionsBaltimoreUSA
  7. 7.Departments of Pathology, Oncology and Surgery, The Sol Goldman Pancreatic Cancer Research CenterJohns Hopkins Medical InstitutionsBaltimoreUSA

Personalised recommendations