Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk

Marc J. Gunter, Tao Wang, Mary Cushman, Xiaonan Xue, Sylvia Wassertheil-Smoller, Howard D. Strickler, Thomas E. Rohan, Joann E. Manson, Anne McTiernan, Robert C. Kaplan, Philipp E. Scherer, Rowan T. Chlebowski, Linda Snetselaar, Dan Wang, Gloria Y F Ho

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Abstract

Background: Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited. Methods: In a case-cohort analysis nested within the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels. All statistical tests were two-sided. Results: The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy (HT) use at baseline (P <inf>interaction</inf> =. 003). In a model that controlled for multiple breast cancer risk factors including body mass index (BMI), estradiol, and insulin, CRP level was positively associated with breast cancer risk among HT nonusers (hazard ratio for high vs low CRP levels = 1.67, 95% confidence interval = 1.04 to 2.68, P <inf>trend</inf> =. 029). None of the other adipokines were statistically significantly associated with breast cancer risk. Following inclusion of CRP, insulin, and estradiol in a multivariable model, the association of BMI with breast cancer was attenuated by 115%. Conclusion: These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity-breast cancer relation.

Original languageEnglish (US)
Article numberdjv169
JournalJournal of the National Cancer Institute
Volume107
Issue number9
DOIs
StatePublished - Sep 1 2015

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Adipokines
Breast Neoplasms
C-Reactive Protein
Insulin
Estradiol
Hormones
Body Mass Index
Obesity
Resistin
Adiponectin
Plasminogen Activator Inhibitor 1
Women's Health
Leptin
Observational Studies
Blood Proteins
Interleukin-6
Estrogens
Cohort Studies
Therapeutics
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gunter, M. J., Wang, T., Cushman, M., Xue, X., Wassertheil-Smoller, S., Strickler, H. D., ... Ho, G. Y. F. (2015). Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk. Journal of the National Cancer Institute, 107(9), [djv169]. https://doi.org/10.1093/jnci/djv169

Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk. / Gunter, Marc J.; Wang, Tao; Cushman, Mary; Xue, Xiaonan; Wassertheil-Smoller, Sylvia; Strickler, Howard D.; Rohan, Thomas E.; Manson, Joann E.; McTiernan, Anne; Kaplan, Robert C.; Scherer, Philipp E.; Chlebowski, Rowan T.; Snetselaar, Linda; Wang, Dan; Ho, Gloria Y F.

In: Journal of the National Cancer Institute, Vol. 107, No. 9, djv169, 01.09.2015.

Research output: Contribution to journalArticle

Gunter, MJ, Wang, T, Cushman, M, Xue, X, Wassertheil-Smoller, S, Strickler, HD, Rohan, TE, Manson, JE, McTiernan, A, Kaplan, RC, Scherer, PE, Chlebowski, RT, Snetselaar, L, Wang, D & Ho, GYF 2015, 'Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk', Journal of the National Cancer Institute, vol. 107, no. 9, djv169. https://doi.org/10.1093/jnci/djv169
Gunter MJ, Wang T, Cushman M, Xue X, Wassertheil-Smoller S, Strickler HD et al. Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk. Journal of the National Cancer Institute. 2015 Sep 1;107(9). djv169. https://doi.org/10.1093/jnci/djv169
Gunter, Marc J. ; Wang, Tao ; Cushman, Mary ; Xue, Xiaonan ; Wassertheil-Smoller, Sylvia ; Strickler, Howard D. ; Rohan, Thomas E. ; Manson, Joann E. ; McTiernan, Anne ; Kaplan, Robert C. ; Scherer, Philipp E. ; Chlebowski, Rowan T. ; Snetselaar, Linda ; Wang, Dan ; Ho, Gloria Y F. / Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 9.
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