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Plasma Adiponectin Levels and Endometrial Cancer Risk in Pre- and Postmenopausal Women

Nutrition and Hormones Unit (A.E.C., R.K., S.Ri., L.D., N.S., M.J.), International Agency for Research on Cancer, 69372 Lyon, France; School of Public Health (A.E.C.), University of Sydney, Sydney 2006, Australia; Université Claude Bernard Lyon 1 (A.E.C.), 69622 Lyon, France; Division of Population Health and Information (C.F.), Alberta Cancer Board, Calgary, Alberta, Canada T2N 4N2; Center for Research in Human Nutrition Rhône-Alpes (F.Bo., M.L.), University of Lyon 1, 69622 Lyon, France; Unité Mixte de Recherche, Institut National de la Santé et de la Recherche Médicale U449/Institut National de la Recherche Agronomique 1235 (F.Bo., M.L.), Lyon, France; Department of Obstetrics and Gynecology (A.L.), New York University School of Medicine, New York, New York 10016; Department of Pathology (E.L.), Umeå University, SE-901 87 Umeå, Sweden; Institute of Cancer Epidemiology (A.Tj., A.O.), Danish Cancer Society, DK-2100 Copenhagen, Denmark; Department of Clinical Epidemiology (K.O.), Aarhus University Hospital, DK-8000 C Aalborg, Denmark; Institut National de la Santé et de la Recherche Médicale (F.C.-C., S.M., V.J.), Institut Gustave Roussy, 94805 Villejuif, France; German Cancer Research Center (R.K., J.L., S.Ro.), 69120 Heidelberg, Germany; German Institute of Human Nutrition (T.P., H.B.), Potsdam-Rehbrücke, 14558 Nuthetal, Germany; University of Athens Medical School (D.T., A.Tr., V.B.), Athens 11527, Greece; Department of Molecular and Nutritional Epidemiology (D.P.), CSPO-Scientific Institute of Tuscany, 50135 Florence, Italy; Epidemiology Unit (F.Be.), Istituto Nazionale Tumori, 20133 Milan, Italy; Cancer Registry (R.T.), Azienda Ospedaliera "Civile M.P. Arezzo," 98158 Ragusa, Italy; CPO-Piemonte (C.S.), 10126 Torino, Italy; Dipartimento di Medicina Clinica e Sperimentale (A.M.), Federico II University of Naples, 80131 Naples, Italy; Public Health and Health Planning Directorate (J.R.Q.), Asturias, Spain; Institut d’Investigació Biomèdica de Bellvitge (M.A.M.), Catalan Institute of Oncology, 08907 Barcelona, Spain; Andalusian School of Public Health (M.-J.S.), Granada, Spain; Public Health Department of Gipuzkoa (N.L.), Basque Government; Epidemiology Department (M.J.T.), Health Council of Murcia, 30008 Murcia, Spain; Public Health Institute of Navarra (E.A.), Pamplona, Spain; National Institute of Public Health and the Environment (H.B.B.-d.M.), 3720 BA Bilthoven, The Netherlands; Julius Center for Health Sciences and Primary Care (P.H.M.P., C.H.v.G.), University Medical Center, 3508 CX Utrecht, The Netherlands; Clinical Gerontology (K.-T.K.), Medical Research Council Centre for Nutritional Epidemiology in Cancer Prevention and Survival (S.B.), Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 1TN, United Kingdom; Medical Research Council Dunn Human Nutrition Unit (S.B.), Cambridge CB2 2XY, United Kingdom; Cancer Research U.K. Epidemiology Unit (N.A., T.K.), University of Oxford, Oxford OX3 7LF, United Kingdom; and Department of Epidemiology and Public Health (E.R.), Imperial College London, London SW7 2AZ, United Kingdom

Address all correspondence and requests for reprints to: Professor Rudolf Kaaks, German National Cancer Center (DKFZ), Division of Cancer Epidemiology, 69120 Heidelberg, Germany. E-mail: r.kaaks{at}dkfz.de.

Background: Adiponectin, an adipocytokine secreted by adipose tissue, is decreased in obesity, insulin resistance, type 2 diabetes, and polycystic ovary syndrome, all of which are well-established risk factors for endometrial cancer.

Methods: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition to examine the relation between prediagnostic plasma adiponectin levels and endometrial cancer risk. Among pre- and postmenopausal women who were not currently using exogenous hormones, 284 women developed incident endometrial cancer during an average of 5.1 yr of follow-up. Using risk set sampling, 548 control subjects were selected, matched on center, age, menopausal status, phase of menstrual cycle, time of blood draw, and fasting status. Conditional logistic regression models were used to estimate relative risks and 95% confidence intervals.

Results: Adiponectin levels were inversely associated with endometrial cancer risk [body mass index-adjusted relative risk for the top vs. bottom quartile = 0.56 (95% confidence interval 0.36–0.86), P_trend = 0.006]. There was evidence of a stronger inverse association among obese women than among nonobese women (P_{heterogeneity} = 0.03). The inverse association also appeared stronger for women who were postmenopausal or perimenopausal than premenopausal at baseline, but this was not statistically significantly heterogeneous (P_{heterogeneity} = 0.51). The association remained statistically significant after separate adjustment for other obesity-related physiological risk factors such as C-peptide, IGF binding protein-1, IGF binding protein-2, SHBG, estrone, or free testosterone but only marginally statistically significant after simultaneous adjustment for these factors.

Conclusions: High circulating adiponectin levels are associated with reduced endometrial cancer risk, largely independent of other obesity-related risk factors.

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