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Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk.

AbstractBACKGROUND:
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 interaction = .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 trend = .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.
AuthorsMarc 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
JournalJournal of the National Cancer Institute (J Natl Cancer Inst) Vol. 107 Issue 9 (Sep 2015) ISSN: 1460-2105 [Electronic] United States
PMID26185195 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, N.I.H., Extramural)
Copyright© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected].
Chemical References
  • Adipokines
  • Adiponectin
  • Biomarkers, Tumor
  • HGF protein, human
  • Insulin
  • Interleukin-6
  • Leptin
  • Plasminogen Activator Inhibitor 1
  • Resistin
  • SERPINE1 protein, human
  • Tumor Necrosis Factor-alpha
  • Estradiol
  • Hepatocyte Growth Factor
  • C-Reactive Protein
Topics
  • Adipokines (blood)
  • Adiponectin (blood)
  • Aged
  • Biomarkers, Tumor (blood)
  • Body Mass Index
  • Breast Neoplasms (blood, epidemiology, etiology)
  • C-Reactive Protein (metabolism)
  • Estradiol (blood)
  • Female
  • Hepatocyte Growth Factor (blood)
  • Humans
  • Inflammation (blood, complications)
  • Insulin (blood)
  • Interleukin-6 (blood)
  • Leptin (blood)
  • Middle Aged
  • Obesity (blood, complications)
  • Odds Ratio
  • Plasminogen Activator Inhibitor 1 (blood)
  • Postmenopause
  • Proportional Hazards Models
  • Prospective Studies
  • Resistin (blood)
  • Risk Assessment
  • Risk Factors
  • Tumor Necrosis Factor-alpha (blood)

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