Artemisia Kakourou1, Charalampia Koutsioumpa1, David S Lopez2,3, Judith Hoffman-Bolton4, Gary Bradwin5, Nader Rifai5, Kathy J Helzlsouer6, Elizabeth A Platz6,7,8, Konstantinos K Tsilidis9,10. 1. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece. 2. Division of Epidemiology, University of Texas School of Public Health, Houston, TX, USA. 3. Division of Urology, University of Texas Medical School, Houston, TX, USA. 4. George W. Comstock Center for Public Health Research and Prevention, Johns Hopkins Bloomberg School of Public Health, Hagerstown, MD, USA. 5. Department of Laboratory Medicine, Harvard Medical School and Children's Hospital, Boston, MA, USA. 6. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 7. Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 8. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. 9. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece. ktsilidi@cc.uoi.gr. 10. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. ktsilidi@cc.uoi.gr.
Abstract
PURPOSE: The 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. METHODS: Colorectal 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. RESULTS: Participants 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; I (2) 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54-0.88; I (2) 0 %), but there was evidence for small-study effects (p 0.02). CONCLUSION: Our 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.
PURPOSE: The 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. METHODS:Colorectal 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. RESULTS:Participants 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; I (2) 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54-0.88; I (2) 0 %), but there was evidence for small-study effects (p 0.02). CONCLUSION: Our 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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