Circulating Soluble Cytokine Receptors and Colorectal Cancer Risk.

Publication Type:

Journal Article

Source:

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (2013)

Keywords:

2013, November 2013, Public Health Sciences Division

Abstract:

Background: Soluble cytokine receptors and receptor antagonist of proinflammatory cytokines can modify cytokine signaling and may affect cancer risk. Methods: In a case-cohort study nested within the Women's Health Initiative cohort of postmenopausal women, we assessed the associations of plasma levels of IL-1 receptor antagonist (IL-1Ra) and the soluble receptors of IL-1 (sIL-1R2), IL-6 (sIL-6R and sgp130), and TNF (sTNFR1 and sTNFR2) with risk of colorectal cancer in 433 cases and 821 subcohort subjects. Baseline levels of estradiol, insulin, leptin, IL-6, and TNF-α measured previously were also available for data analysis. Results: After adjusting for significant covariates - including age, race, smoking, colonoscopy history, waist circumference, and levels of estrogen, insulin, and leptin - relatively high levels of sIL-6R and sIL-1R2 were associated with reduced colorectal cancer risk [hazard ratios comparing extreme quartiles (HRQ4-Q1) for sIL-6R = 0.56, 95% CI = 0.38-0.83; HRQ4-Q1 for sIL-1R2 = 0.44, 95% CI = 0.29-0.67]. The associations with IL-1Ra, sgp130, sTNFR1, and sTNFR2 were null. The inverse association of sIL-1R2 with colorectal cancer risk persisted in cases diagnosed ≤ 5 and >5 years from baseline blood draw; the association with sIL-6R, however, was not evident in the latter group, possibly indicating that relatively low levels of sIL-6R in cases might be due to undiagnosed cancer at the time of blood draw. Conclusions: High circulating levels of sIL-1R2 may be protective against colorectal carcinogenesis and/or be a marker of reduced risk for the disease. Impact: sIL-1R2 has potential to be a chemopreventive and/or immunotherapeutic agent.