TY - JOUR
T1 - Circulating soluble cytokine receptors and colorectal cancer risk
AU - Ho, Gloria Y.F.
AU - Wang, Tao
AU - Zheng, Siqun L.
AU - Tinker, Lesley
AU - Xu, Jianfeng
AU - Rohan, Thomas E.
AU - Wassertheil-Smoller, Sylvia
AU - Xue, Xiaonan
AU - Augenlicht, Leonard H.
AU - Peters, Ulrike
AU - Phipps, Amanda I.
AU - Strickler, Howard D.
AU - Gunter, Marc J.
AU - Cushman, Mary
PY - 2014/1
Y1 - 2014/1
N2 - 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 interleukin (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 [HRs comparing extreme quartiles (HRQ4-Q1) for sIL-6R, 0.56; 95% confidence interval (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 in inflammationrelated diseases. Cancer Epidemiol Biomarkers Prev; 23(1); 179-88.
AB - 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 interleukin (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 [HRs comparing extreme quartiles (HRQ4-Q1) for sIL-6R, 0.56; 95% confidence interval (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 in inflammationrelated diseases. Cancer Epidemiol Biomarkers Prev; 23(1); 179-88.
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U2 - 10.1158/1055-9965.EPI-13-0545
DO - 10.1158/1055-9965.EPI-13-0545
M3 - Article
C2 - 24192010
AN - SCOPUS:84892734096
SN - 1055-9965
VL - 23
SP - 179
EP - 188
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -