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Plasma Adiponectin Concentrations and Risk of Incident Breast Cancer

Channing Laboratory, Department of Medicine (S.S.T., A.H.E., G.A.C., W.C.W., S.E.H.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; Departments of Epidemiology (S.S.T., A.H.E., G.A.C., W.C.W., S.E.H.) and Nutrition (W.C.W.), Harvard School of Public Health, Boston, Massachusetts 02115; and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine (T.K., C.S.M.), Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Shelley S. Tworoger, Channing Laboratory, 181 Longwood Avenue, Third Floor, Boston, Massachusetts 02115. E-mail: nhsst{at}channing.harvard.edu.

Introduction: Previous retrospective case-control studies suggest that adiponectin, an obesity-related hormone, is inversely associated with breast cancer risk, particularly in postmenopausal women; however, no prospective studies exist. Therefore, we conducted a prospective case-control study nested within the Nurses’ Health Study (NHS) and NHSII cohorts examining the association between plasma adiponectin concentrations and breast cancer risk.

Materials and Methods: Blood samples were collected from 1989 through 1990 (NHS) and 1996 through 1999 (NHSII); adiponectin was measured by RIA. The analysis included 1477 breast cancer cases diagnosed after blood collection and before June 2000 (NHS) or June 2003 (NHSII) who had one or two controls (n = 2196) matched on age, menopausal status, postmenopausal hormone (PMH) use, fasting, and time of day and month of blood collection. We adjusted for body mass index at age 18, weight change from age 18 to blood draw, family history of breast cancer, history of benign breast disease, duration of PMH use, ages at menarche and first birth, and parity.

Results: Although we observed no association between adiponectin and breast cancer risk overall, there was a nearly significant interaction by menopausal status (P = 0.08), with a relative risk, top vs. bottom quartile of 0.73 (95% confidence interval, 0.55–0.98; P trend = 0.08) among postmenopausal women and 1.30 (95% confidence interval, 0.80–2.10; P trend = 0.09) for premenopausal women. Among postmenopausal women, adiponectin appeared more strongly inversely associated in women who never used PMH (P heterogeneity = 0.05) and women with low circulating estradiol levels (P heterogeneity = 0.05).

Discussion: Our results suggest that adiponectin may be inversely associated with postmenopausal breast cancer risk, particularly in a low-estrogen environment.

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