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Circulating Levels of Inflammatory Cytokines and Risk of Colorectal Adenomas

¹ Department of Epidemiology, School of Public Health, ² Center for Gastrointestinal Biology and Disease, and ³ Department of Pathology, University of North Carolina, Chapel Hill, North Carolina and ⁴ Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina

Requests for reprints: Robert S. Sandler, University of North Carolina, CB#7555, 4111 Bioinformatics Building, Chapel Hill, NC 27599-7555. Phone: 919-966-0090; Fax: 919-966-2478; E-mail: rsandler{at}med.unc.edu.

The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF- in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF- were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between known risk factors for colorectal neoplasia and circulating levels of inflammatory cytokines and associations between inflammatory cytokines and colorectal adenomas. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines, including older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF- and, to a lesser degree, with CRP. For IL-6, adjusted odds ratios (OR) for colorectal adenomas were 1.79 [95% confidence interval (CI), 1.19–2.69] for the second highest plasma level and 1.85 (95% CI, 1.24–2.75) for the highest level compared with the reference level. A similar association was found with TNF-, with adjusted ORs of 1.56 (95% CI, 1.03–2.36) and 1.66 (95% CI, 1.10–2.52), respectively. Our findings indicate that systemic inflammation might be involved in the early development of colorectal neoplasia. [Cancer Res 2008;68(1):323–8]

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