Circulating soluble cytokine receptors and colorectal cancer risk

Gloria Y F Ho, Tao Wang, Siqun L. Zheng, Lesley Tinker, Jianfeng Xu, Thomas E. Rohan, Sylvia Wassertheil-Smoller, Xiaonan (Nan) Xue, Leonard H. Augenlicht, Ulrike Peters, Amanda I. Phipps, Howard Strickler, Marc J. Gunter, Mary Cushman

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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 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.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number1
DOIs
StatePublished - Jan 2014

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Cytokine Receptors
Colorectal Neoplasms
Cytokine Receptor gp130
Interleukin-1 Receptors
Leptin
Interleukin-6
Confidence Intervals
Insulin
Cytokines
Interleukins
Waist Circumference
Women's Health
Colonoscopy
Tumor Biomarkers
Estradiol
Neoplasms
Estrogens
Carcinogenesis
Cohort Studies
Smoking

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Circulating soluble cytokine receptors and colorectal cancer risk. / Ho, Gloria Y F; Wang, Tao; Zheng, Siqun L.; Tinker, Lesley; Xu, Jianfeng; Rohan, Thomas E.; Wassertheil-Smoller, Sylvia; Xue, Xiaonan (Nan); Augenlicht, Leonard H.; Peters, Ulrike; Phipps, Amanda I.; Strickler, Howard; Gunter, Marc J.; Cushman, Mary.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 23, No. 1, 01.2014, p. 179-188.

Research output: Contribution to journalArticle

Ho, GYF, Wang, T, Zheng, SL, Tinker, L, Xu, J, Rohan, TE, Wassertheil-Smoller, S, Xue, XN, Augenlicht, LH, Peters, U, Phipps, AI, Strickler, H, Gunter, MJ & Cushman, M 2014, 'Circulating soluble cytokine receptors and colorectal cancer risk', Cancer Epidemiology Biomarkers and Prevention, vol. 23, no. 1, pp. 179-188. https://doi.org/10.1158/1055-9965.EPI-13-0545
Ho, Gloria Y F ; Wang, Tao ; Zheng, Siqun L. ; Tinker, Lesley ; Xu, Jianfeng ; Rohan, Thomas E. ; Wassertheil-Smoller, Sylvia ; Xue, Xiaonan (Nan) ; Augenlicht, Leonard H. ; Peters, Ulrike ; Phipps, Amanda I. ; Strickler, Howard ; Gunter, Marc J. ; Cushman, Mary. / Circulating soluble cytokine receptors and colorectal cancer risk. In: Cancer Epidemiology Biomarkers and Prevention. 2014 ; Vol. 23, No. 1. pp. 179-188.
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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 (Nan)

AU - Augenlicht, Leonard H.

AU - Peters, Ulrike

AU - Phipps, Amanda I.

AU - Strickler, Howard

AU - Gunter, Marc J.

AU - Cushman, Mary

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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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