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

  1. Sabina Rinaldi1,
  2. Laure Dossus1,2,
  3. Annekatrin Lukanova2,3,
  4. Petra H.M. Peeters4,
  5. Naomi E. Allen5,
  6. Timothy Key5,
  7. Sheila Bingham6,
  8. Kay-Tee Khaw7,
  9. Dimitrios Trichopoulos8,
  10. Antonia Trichopoulou8,
  11. Eleni Oikonomou8,
  12. Guillem Pera9,
  13. Nerea Larrañaga10,
  14. Carmen Martinez-Garcia11,
  15. Eva Ardanaz12,
  16. J. Ramón Quirós13,
  17. María-José Tormo14,
  18. Anne Tjønneland15,
  19. Anja Olsen15,
  20. Kim Overvad16,
  21. Jenny Chang-Claude2,
  22. Jakob Linseisen2,
  23. Mandy Schulz17,
  24. Heiner Boeing17,
  25. Carla H. van Gils4,
  26. Bas H. Bueno-de-Mesquita18,
  27. Valeria Pala19,
  28. Domenico Palli20,
  29. Salvatore Panico21,
  30. Rosario Tumino22,
  31. Paolo Vineis23,
  32. Françoise Clavel-Chapelon25,
  33. Sylvie Mesrine25,
  34. Marie-Christine Boutron-Ruault25,
  35. Eva Lundin26,
  36. Åsa Ågren27,
  37. Göran Berglund28,
  38. Jonas Manjer29,
  39. Merethe Kumle30,
  40. Eiliv Lund30,
  41. Nadia Slimani1,
  42. Rodolfo Saracci1,
  43. Elio Riboli24 and
  44. Rudolf Kaaks1,2
  1. 1IARC, Lyon, France; 2German Cancer Research Centre, Clinical Epidemiology, Heidelberg, Germany; 3New York University School of Medicine, New York, New York; 4Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; 5Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, United Kingdom; 6Medical Research Council Centre for Nutrition in Cancer Prevention and Survival, Department of Public Health and Primary Care, University of Cambridge; 7Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom; 8Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Athens, Greece; 9Epidemiology Department, Catalan Institute of Oncology, Barcelona, Spain; 10Public Health Division of Gipuzkoa, Health Department of the Basque Country, Donostia-San Sebastian, Spain; 11Andalusian School of Public Health, Granada, Spain; 12Public Health Institute of Navarra, Pamplona, Spain; 13Public Health and Health Planning Directorate, Asturias, Spain; 14Consejería de Sanida, Murcia, Spain; 15Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; 16Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark; 17Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; 18Centre for Nutrition and Health, National Institute of Public Health and the Environment, Bilthoven, the Netherlands; 19Nutritional Epidemiology Unit, National Cancer Institute, Milan, Italy; 20Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Center, Scientific Institute of Tuscany, Florence, Italy; 21Dipartimento di Medicina Clinica e Sperimentale, Università Federico II, Naples, Italy; 22Cancer Registry, Azienda Ospedaliera “Civile M.P. Arezzo,” Ragusa, Italy; 23Environmental Epidemiology and 24Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom; 25Institut National de la Santé et de la Recherche Médicale, Institut Gustave Roussy, Villejuif, France; Departments of 26Medical Biosciences/Pathology and 27Public Health and Clinical Medicine, University of Umeå, Umeå, Sweden; Departments of 28Clinical Sciences and 29Surgery, Malmö University Hospital, Malmö, Sweden; and 30Institute of Community Medicine, University of Tromso, Tromso, Norway
  1. 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

Abstract

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); Ptrend = 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)

Footnotes

  • Grant support: The European Prospective Investigation into Cancer and Nutrition study was funded by “Europe Against Cancer” Programme of the European Commission (SANCO); Ligue contre le Cancer (France); Société 3M (France); Mutuelle Générale de l'Education Nationale; Institut National de la Santé et de la Recherche Médicale; German Cancer Aid; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health (RCESP-C03/09); the participating regional governments and institutions of Spain; Cancer Research UK; Medical Research Council, United Kingdom; the Stroke Association, United Kingdom; British Heart Foundation; Department of Health, United Kingdom; Food Standards Agency, United Kingdom; the Wellcome Trust, United Kingdom; Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer (AICR); Dutch Ministry of Public Health, Welfare, and Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research Funds; Dutch Zorg Onderzoek Nederland (ZON); World Cancer Research Fund (WCRF); Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Norwegian Cancer Society.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted November 8, 2006.
    • Received September 6, 2006.
    • Revision received October 18, 2006.
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  1. doi: 10.1158/1055-9965.EPI-06-0755 Cancer Epidemiology, Biomarkers & Prevention January 1, 2007 16, 23
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