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Gaudet MM , Falk RT , Gierach GL , Lacey JV , Graubard BI , Dorgan JF , Brinton LA
Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women?
Cancer Epidemiology. 2010 Oct;34(5) :580-586
PMID: ISI:000283974700011   
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Introduction: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Methods: Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Results: Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r = 0.26, p-value = 0.033; r = 0.42, p = 0.0003), decreasing levels of sex hormone binding globulin (r = 0.38, p = 0.0013; r = 0.32, p = 0.0076), and increasing body mass index (BMI) (r = 0.31, p = <0.0001: r = 0.39, p = <0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p = 0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend = 0.43), aPAI-1 (p = 0.78), or resistin (p = 0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p > 0.05). The lack of association with risk may be due to measurement error of the laboratory assays. Discussion: lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk. (C) 2010 Elsevier Ltd. All rights reserved.
Gaudet, Mia M. Falk, Roni T. Gierach, Gretchen L. Lacey, James V., Jr. Graubard, Barry I. Dorgan, Joanne F. Brinton, Louise A. 26 Elsevier sci ltd; the boulevard, langford lane, kidlington, oxford ox5 1gb, oxon, england 677fo