title: Interleukin-6 and risk of colorectal cancer: results from the CLUE II cohort and a meta-analysis of prospective studies.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece.
authors.forename: Artemisia
authors.initials: A
authors.lastname: Kakourou
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece.
authors.forename: Charalampia
authors.initials: C
authors.lastname: Koutsioumpa
authors.affiliation: Division of Epidemiology, University of Texas School of Public Health, Houston, TX, USA.|Division of Urology, University of Texas Medical School, Houston, TX, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Lopez
authors.affiliation: George W. Comstock Center for Public Health Research and Prevention, Johns Hopkins Bloomberg School of Public Health, Hagerstown, MD, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Hoffman-Bolton
authors.affiliation: Department of Laboratory Medicine, Harvard Medical School and Children's Hospital, Boston, MA, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Bradwin
authors.affiliation: Department of Laboratory Medicine, Harvard Medical School and Children's Hospital, Boston, MA, USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Helzlsouer
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece. ktsilidi@cc.uoi.gr.|Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. ktsilidi@cc.uoi.gr.
authors.forename: Konstantinos K
authors.initials: KK
authors.lastname: Tsilidis
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: Cohort study; Colorectal cancer; Inflammation; Meta-analysis