TY - JOUR
T1 - Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk
AU - Gunter, Marc J.
AU - Wang, Tao
AU - Cushman, Mary
AU - Xue, Xiaonan
AU - Wassertheil-Smoller, Sylvia
AU - Strickler, Howard D.
AU - Rohan, Thomas E.
AU - Manson, Joann E.
AU - McTiernan, Anne
AU - Kaplan, Robert C.
AU - Scherer, Philipp E.
AU - Chlebowski, Rowan T.
AU - Snetselaar, Linda
AU - Wang, Dan
AU - Ho, Gloria Y F
N1 - Publisher Copyright:
© 2015 The Author.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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 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.
AB - 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 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.
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U2 - 10.1093/jnci/djv169
DO - 10.1093/jnci/djv169
M3 - Article
C2 - 26389154
AN - SCOPUS:84942245589
SN - 0027-8874
VL - 107
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 9
ER -