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Endogenous Androgens and Risk of Epithelial Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

¹ IARC, Lyon, France; ² German Cancer Research Centre, Clinical Epidemiology, Heidelberg, Germany; ³ New York University School of Medicine, New York, New York; ⁴ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; ⁵ Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, United Kingdom; ⁶ Medical Research Council Centre for Nutrition in Cancer Prevention and Survival, Department of Public Health and Primary Care, University of Cambridge; ⁷ Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom; ⁸ Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Athens, Greece; ⁹ Epidemiology Department, Catalan Institute of Oncology, Barcelona, Spain; ¹⁰ Public Health Division of Gipuzkoa, Health Department of the Basque Country, Donostia-San Sebastian, Spain; ¹¹ Andalusian School of Public Health, Granada, Spain; ¹² Public Health Institute of Navarra, Pamplona, Spain; ¹³ Public Health and Health Planning Directorate, Asturias, Spain; ¹⁴ Consejería de Sanida, Murcia, Spain; ¹⁵ Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; ¹⁶ Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark; ¹⁷ Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; ¹⁸ Centre for Nutrition and Health, National Institute of Public Health and the Environment, Bilthoven, the Netherlands; ¹⁹ Nutritional Epidemiology Unit, National Cancer Institute, Milan, Italy; ²⁰ Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Center, Scientific Institute of Tuscany, Florence, Italy; ²¹ Dipartimento di Medicina Clinica e Sperimentale, Università Federico II, Naples, Italy; ²² Cancer Registry, Azienda Ospedaliera "Civile M.P. Arezzo," Ragusa, Italy; ²³ Environmental Epidemiology and ²⁴ Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom; ²⁵ Institut National de la Santé et de la Recherche Médicale, Institut Gustave Roussy, Villejuif, France; Departments of ²⁶ Medical Biosciences/Pathology and ²⁷ Public Health and Clinical Medicine, University of Umeå, Umeå, Sweden; Departments of ²⁸ Clinical Sciences and ²⁹ Surgery, Malmö University Hospital, Malmö, Sweden; and ³⁰ Institute of Community Medicine, University of Tromso, Tromso, Norway

Requests for reprints: Rudolf Kaaks, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69121 Heidelberg, Germany. Phone: 49-6221-422385; Fax: 49-6221-422203. E-mail: r.kaaks{at}dkfz.de

Few epidemiologic studies have examined the hypothesis that circulating androgens are involved in the development of ovarian cancer. We investigated the association between prediagnostic serum levels of androgens and sex hormone–binding globulin (SHBG) and ovarian cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort. One hundred and ninety-two ovarian cancer cases and 346 matched controls not using exogenous hormones at baseline blood donation were eligible for the study. Serum levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and SHBG were measured by direct immunoassays. Free testosterone (fT) was calculated according to mass action laws. Multivariate conditional logistic regression was used to estimate odds ratios adjusted for possible confounders. Overall, there was no association between serum concentrations of androgens or SHBG and ovarian cancer risk. In postmenopausal women, fT concentrations were inversely related to risk [highest versus lowest tertile odds ratio 0.45 (0.24-0.86); P_trend = 0.01]. Among women diagnosed before the age of 55 years, there was a negative association with SHBG and a positive association with fT and ovarian cancer risk, although these associations were not statistically significant. The present study suggests that circulating androgens and SHBG levels are not strongly associated with ovarian cancer risk, although levels of fT may be associated with an increased risk among women diagnosed at relatively young age. The heterogeneity of results on the associations of fT with ovarian cancer risk in postmenopausal women deserves further investigation. (Cancer Epidemiol Biomarkers Prev 2007;16(1):23–9)

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