A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers

Tao Wang, Thomas E. Rohan, Marc J. Gunter, Xiaonan Xue, Jean Wactawski-Wende, Swapnil N. Rajpathak, Mary Cushman, Howard D. Strickler, Robert C. Kaplan, Sylvia Wassertheil-Smoller, Philipp E. Scherer, Gloria Y F Ho

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Abstract

Background: It is hypothesized that inflammation may mediate the relationship between obesity and endometrial cancer risk. We examined the associations of three inflammation markers, C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, with risk of endometrial cancer. Methods: A case-cohort study was nested within the Women's Health Initiative, a cohort of postmenopausal women. Baseline plasma samples of 151 incident endometrial cancer cases and 301 subcohort subjects not using hormones were assayed. Results: CRP, but not IL-6 or TNF-α, was positively associated with endometrial cancer risk after adjusting for age and BMI [HR comparing extreme quartiles (HR q4-q1) = 2.29; 95% CI = 1.13-4.65; Ptrend = 0.012). After additional adjustment for estradiol and insulin, this association was attenuated (HRq4-q1 = 1.70; 95% CI = 0.78-3.68; Ptrend = 0.127). Obesity (BMI ≥ 30 kg/m2) was associated with endometrial cancer risk in an ageadjusted model. The obesity effect was reduced by 48%, 67%, and 77% when either estradiol, CRP, or insulin, respectively, was included in the model, and it became null when all three factors were adjusted for simultaneously. Conclusions: The association between inflammation, as indicated by a relatively high level of CRP, and endometrial cancer risk may partially be explained by hyperinsulinemia and elevated estradiol. Nevertheless, all three factors contribute to and mediate the link between obesity and endometrial cancer in postmenopausal women not using hormones. Impact: The association between obesity and endometrial cancer risk in postmenopausal women may be attributed to inflammation, insulin resistance, and elevated estrogen.

Original languageEnglish (US)
Pages (from-to)971-977
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume20
Issue number5
DOIs
StatePublished - May 2011

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Endometrial Neoplasms
Hormones
Prospective Studies
Inflammation
Obesity
C-Reactive Protein
Estradiol
Interleukin-6
Tumor Necrosis Factor-alpha
Insulin
Hyperinsulinism
Women's Health
Insulin Resistance
Estrogens
Cohort Studies

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Wang, T., Rohan, T. E., Gunter, M. J., Xue, X., Wactawski-Wende, J., Rajpathak, S. N., ... Ho, G. Y. F. (2011). A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers. Cancer Epidemiology Biomarkers and Prevention, 20(5), 971-977. https://doi.org/10.1158/1055-9965.EPI-10-1222

A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers. / Wang, Tao; Rohan, Thomas E.; Gunter, Marc J.; Xue, Xiaonan; Wactawski-Wende, Jean; Rajpathak, Swapnil N.; Cushman, Mary; Strickler, Howard D.; Kaplan, Robert C.; Wassertheil-Smoller, Sylvia; Scherer, Philipp E.; Ho, Gloria Y F.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 5, 05.2011, p. 971-977.

Research output: Contribution to journalArticle

Wang, T, Rohan, TE, Gunter, MJ, Xue, X, Wactawski-Wende, J, Rajpathak, SN, Cushman, M, Strickler, HD, Kaplan, RC, Wassertheil-Smoller, S, Scherer, PE & Ho, GYF 2011, 'A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers', Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 5, pp. 971-977. https://doi.org/10.1158/1055-9965.EPI-10-1222
Wang, Tao ; Rohan, Thomas E. ; Gunter, Marc J. ; Xue, Xiaonan ; Wactawski-Wende, Jean ; Rajpathak, Swapnil N. ; Cushman, Mary ; Strickler, Howard D. ; Kaplan, Robert C. ; Wassertheil-Smoller, Sylvia ; Scherer, Philipp E. ; Ho, Gloria Y F. / A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers. In: Cancer Epidemiology Biomarkers and Prevention. 2011 ; Vol. 20, No. 5. pp. 971-977.
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abstract = "Background: It is hypothesized that inflammation may mediate the relationship between obesity and endometrial cancer risk. We examined the associations of three inflammation markers, C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, with risk of endometrial cancer. Methods: A case-cohort study was nested within the Women's Health Initiative, a cohort of postmenopausal women. Baseline plasma samples of 151 incident endometrial cancer cases and 301 subcohort subjects not using hormones were assayed. Results: CRP, but not IL-6 or TNF-α, was positively associated with endometrial cancer risk after adjusting for age and BMI [HR comparing extreme quartiles (HR q4-q1) = 2.29; 95{\%} CI = 1.13-4.65; Ptrend = 0.012). After additional adjustment for estradiol and insulin, this association was attenuated (HRq4-q1 = 1.70; 95{\%} CI = 0.78-3.68; Ptrend = 0.127). Obesity (BMI ≥ 30 kg/m2) was associated with endometrial cancer risk in an ageadjusted model. The obesity effect was reduced by 48{\%}, 67{\%}, and 77{\%} when either estradiol, CRP, or insulin, respectively, was included in the model, and it became null when all three factors were adjusted for simultaneously. Conclusions: The association between inflammation, as indicated by a relatively high level of CRP, and endometrial cancer risk may partially be explained by hyperinsulinemia and elevated estradiol. Nevertheless, all three factors contribute to and mediate the link between obesity and endometrial cancer in postmenopausal women not using hormones. Impact: The association between obesity and endometrial cancer risk in postmenopausal women may be attributed to inflammation, insulin resistance, and elevated estrogen.",
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T1 - A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers

AU - Wang, Tao

AU - Rohan, Thomas E.

AU - Gunter, Marc J.

AU - Xue, Xiaonan

AU - Wactawski-Wende, Jean

AU - Rajpathak, Swapnil N.

AU - Cushman, Mary

AU - Strickler, Howard D.

AU - Kaplan, Robert C.

AU - Wassertheil-Smoller, Sylvia

AU - Scherer, Philipp E.

AU - Ho, Gloria Y F

PY - 2011/5

Y1 - 2011/5

N2 - Background: It is hypothesized that inflammation may mediate the relationship between obesity and endometrial cancer risk. We examined the associations of three inflammation markers, C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, with risk of endometrial cancer. Methods: A case-cohort study was nested within the Women's Health Initiative, a cohort of postmenopausal women. Baseline plasma samples of 151 incident endometrial cancer cases and 301 subcohort subjects not using hormones were assayed. Results: CRP, but not IL-6 or TNF-α, was positively associated with endometrial cancer risk after adjusting for age and BMI [HR comparing extreme quartiles (HR q4-q1) = 2.29; 95% CI = 1.13-4.65; Ptrend = 0.012). After additional adjustment for estradiol and insulin, this association was attenuated (HRq4-q1 = 1.70; 95% CI = 0.78-3.68; Ptrend = 0.127). Obesity (BMI ≥ 30 kg/m2) was associated with endometrial cancer risk in an ageadjusted model. The obesity effect was reduced by 48%, 67%, and 77% when either estradiol, CRP, or insulin, respectively, was included in the model, and it became null when all three factors were adjusted for simultaneously. Conclusions: The association between inflammation, as indicated by a relatively high level of CRP, and endometrial cancer risk may partially be explained by hyperinsulinemia and elevated estradiol. Nevertheless, all three factors contribute to and mediate the link between obesity and endometrial cancer in postmenopausal women not using hormones. Impact: The association between obesity and endometrial cancer risk in postmenopausal women may be attributed to inflammation, insulin resistance, and elevated estrogen.

AB - Background: It is hypothesized that inflammation may mediate the relationship between obesity and endometrial cancer risk. We examined the associations of three inflammation markers, C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, with risk of endometrial cancer. Methods: A case-cohort study was nested within the Women's Health Initiative, a cohort of postmenopausal women. Baseline plasma samples of 151 incident endometrial cancer cases and 301 subcohort subjects not using hormones were assayed. Results: CRP, but not IL-6 or TNF-α, was positively associated with endometrial cancer risk after adjusting for age and BMI [HR comparing extreme quartiles (HR q4-q1) = 2.29; 95% CI = 1.13-4.65; Ptrend = 0.012). After additional adjustment for estradiol and insulin, this association was attenuated (HRq4-q1 = 1.70; 95% CI = 0.78-3.68; Ptrend = 0.127). Obesity (BMI ≥ 30 kg/m2) was associated with endometrial cancer risk in an ageadjusted model. The obesity effect was reduced by 48%, 67%, and 77% when either estradiol, CRP, or insulin, respectively, was included in the model, and it became null when all three factors were adjusted for simultaneously. Conclusions: The association between inflammation, as indicated by a relatively high level of CRP, and endometrial cancer risk may partially be explained by hyperinsulinemia and elevated estradiol. Nevertheless, all three factors contribute to and mediate the link between obesity and endometrial cancer in postmenopausal women not using hormones. Impact: The association between obesity and endometrial cancer risk in postmenopausal women may be attributed to inflammation, insulin resistance, and elevated estrogen.

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