Authors' Affiliations: Departments of Epidemiology and Population Health and Medicine, Albert Einstein College of Medicine, Bronx, New York; Center for Genomics and Personalized Medicine Research, Wake Forest University, Winston-Salem, North Carolina; Public Health Sciences Division, Fred Hutchinson Cancer Research Center; University of Washington, Seattle, Washington; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; and Departments of Medicine and Pathology, University of Vermont, Burlington, Vermont.
Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):179-88. doi: 10.1158/1055-9965.EPI-13-0545. Epub 2013 Nov 5.
Soluble cytokine receptors and receptor antagonist of proinflammatory cytokines can modify cytokine signaling and may affect cancer risk.
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.
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.
High circulating levels of sIL-1R2 may be protective against colorectal carcinogenesis and/or be a marker of reduced risk for the disease.
sIL-1R2 has potential to be a chemopreventive and/or immunotherapeutic agent in inflammation-related diseases.
促炎细胞因子的可溶性细胞因子受体和受体拮抗剂可调节细胞因子信号转导，并可能影响癌症风险。
在绝经后妇女妇女健康倡议队列的病例-对照研究中，我们评估了白细胞介素（IL）-1 受体拮抗剂（IL-1Ra）和 IL-1 的可溶性受体（sIL-1R2）、IL-6（sIL-6R 和 sgp130）以及 TNF（sTNFR1 和 sTNFR2）在 433 例病例和 821 例亚组人群中的血浆水平与结直肠癌风险之间的关系。之前还可以进行分析的数据包括基线水平的雌二醇、胰岛素、瘦素、IL-6 和 TNF-α。
调整了重要协变量后，包括年龄、种族、吸烟、结肠镜检查史、腰围以及雌激素、胰岛素和瘦素水平，相对较高的 sIL-6R 和 sIL-1R2 与结直肠癌风险降低相关[极端四分位（HRQ4-Q1）的 HRs 比较 sIL-6R，0.56；95%置信区间（CI），0.38-0.83；HRQ4-Q1 为 sIL-1R2，0.44；95%CI，0.29-0.67]。与 IL-1Ra、sgp130、sTNFR1 和 sTNFR2 的关联为零。sIL-1R2 与结直肠癌风险的负相关在基线血液采集后≤5 年和>5 年诊断的病例中仍然存在；然而，sIL-6R 与后者的关联并不明显，这可能表明在采血时，病例中相对较低的 sIL-6R 可能是由于未确诊的癌症。
高水平的循环 sIL-1R2 可能对结直肠癌的发生具有保护作用，或者是疾病风险降低的标志物。
sIL-1R2 具有成为炎症相关疾病的化学预防和/或免疫治疗剂的潜力。
