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Submitted on June 26, 2006
Accepted on October 16, 2006
Nutrition and Hormones Unit, International Agency for Research on Cancer, Lyon, France; School of Public Health, University of Sydney, Australia; Université Claude Bernard Lyon 1, France; Division of Population Health and Information, Alberta Cancer Board, Calgary, Alberta, Canada; Center for Research in Human Nutrition, University of Lyon 1, France; UMR INSERM U449 / INRA 1235, Lyon, France; Department of Obstetrics and Gynecology, New York University School of Medicine, USA; Department of Pathology, Umeå University, Sweden; Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark; INSERM, Institut Gustave Roussy, Villejuif, France; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany; University of Athens Medical School, Athens 11527, Greece; Molecular & Nutritional Epidemiology, CSPO-Scientific Institute of Tuscany, Florence, Italy; Epidemiology Unit, Istituto Nazionale Tumori, Milan, Italy; Cancer Registry, Azienda Ospedaliera "Civile M.P. Arezzo", Ragusa, Italy; CPO-Piemonte, Torino; Dipartimento di Medicina Clinica e Sperimentale, Federico II University of Naples, Italy; Public Health and Health Planning Directorate, Asturias, Spain; IDIBELL, Catalan Institute of Oncology, Barcelona, Spain; Andalusian School of Public Health, Granada, Spain; Public Health Department of Gipuzkoa, Basque Government; Epidemiology Department, Health Council of Murcia, Murcia, Spain; Public Health Institute of Navarra, Pamplona, Spain; National Institute of Public Health and the Environment, Bilthoven, The Netherlands; Julius Center for Health Sciences & Primary Care, University Medical Center, Utrecht, The Netherlands; Clinical Gerontology, Department of Public Health and Primary Care, University of Cambridge, UK; MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival, University of Cambridge, UK; Cancer Research UK Epidemiology Unit, University of Oxford, UK; Department of Epidemiology and Public Health, Imperial College London, UK
* To whom correspondence should be addressed. 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 (EPIC), to examine the relation between prediagnostic plasma adiponectin levels and endometrial cancer risk. Among pre- and post-menopausal 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 (RR) and 95% confidence intervals (CI).
Results: Adiponectin levels were inversely associated with endometrial cancer risk (BMI-adjusted RR for the top vs. bottom quartile = 0.56 [95% CI 0.36-0.86], Ptrend=0.006). There was evidence of a stronger inverse association among obese women than among non-obese women (Pheterogeneity=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 (Pheterogeneity=0.51). The association remained statistically significant after separate adjustment for other obesity-related physiologic risk factors such as C-peptide, IGFBP-1, IGFBP-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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