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Interleukin-6 and risk of colorectal cancer: results from the CLUE II cohort and a meta-analysis of prospective studies

  • Kakourou, Artemisia1
  • Koutsioumpa, Charalampia1
  • Lopez, David S.2, 3
  • Hoffman-Bolton, Judith4
  • Bradwin, Gary5
  • Rifai, Nader5
  • Helzlsouer, Kathy J.6
  • Platz, Elizabeth A.6, 7, 8
  • Tsilidis, Konstantinos K.1, 9
  • 1 University of Ioannina School of Medicine, Department of Hygiene and Epidemiology, Stavros Niarchos Av., University Campus, Ioannina, Greece , Ioannina (Greece)
  • 2 University of Texas School of Public Health, Division of Epidemiology, Houston, TX, USA , Houston (United States)
  • 3 University of Texas Medical School, Division of Urology, Houston, TX, USA , Houston (United States)
  • 4 Johns Hopkins Bloomberg School of Public Health, George W. Comstock Center for Public Health Research and Prevention, Hagerstown, MD, USA , Hagerstown (United States)
  • 5 Harvard Medical School and Children’s Hospital, Department of Laboratory Medicine, Boston, MA, USA , Boston (United States)
  • 6 Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, USA , Baltimore (United States)
  • 7 Johns Hopkins University School of Medicine, Department of Urology and James Buchanan Brady Urological Institute, Baltimore, MD, USA , Baltimore (United States)
  • 8 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA , Baltimore (United States)
  • 9 Imperial College London, Department of Epidemiology and Biostatistics, School of Public Health, London, UK , London (United Kingdom)
Published Article
Cancer Causes & Control
Publication Date
Jul 29, 2015
DOI: 10.1007/s10552-015-0641-1
Springer Nature


PurposeThe association between prediagnostic interleukin-6 (IL-6) concentrations and risk of colorectal cancer was evaluated in a nested case–control study and a meta-analysis of prospective studies.MethodsColorectal cancer cases (n = 173) and matched controls (n = 345) were identified between 1989 and 2000 among participants in the CLUE II cohort of Washington Country, Maryland. Matched odds ratios and the corresponding 95 % confidence intervals (CIs) were estimated using conditional logistic regression models.ResultsParticipants in the highest third of plasma IL-6 concentration had a 2.48 times higher risk of colon cancer compared to participants in the bottom third (95 % CI 1.26–4.87; p-trend 0.02) after multivariate adjustment. This association did not differ according to the stage of disease, age, sex, or other potential modifying variables and remained statistically significant after adjustment for C-reactive protein concentrations. No statistically significant association was observed for rectal cancer risk. The meta-analysis of six prospective studies yielded an increased but borderline statistically significant risk of colon cancer per 1 U increase in naturally logarithm-transformed IL-6 (summary RR 1.22; 95 % CI 1.00–1.49; I2 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54–0.88; I2 0 %), but there was evidence for small-study effects (p 0.02).ConclusionOur findings provide support for a modest positive association between IL-6 concentrations and colon cancer risk. More work is needed to determine whether IL-6 is a valid marker of colorectal inflammation and whether such inflammation contributes to colon and rectal cancer risk.

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