Endogenous Sex Steroids and Risk of Cervical Carcinoma: Results from the EPIC Study

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Abstract

Background: Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC). Methods: Ninety-nine ICC cases, 121 cervical intraepithelial neoplasia grade 3 (CIN3) cases and 2 control women matched with each case for center, age, menopausal status and blood collection-related variables, were identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Circulating levels of testosterone (T) and estradiol (E(2)); dehydroepiandrosterone sulfate (DHEAS); progesterone (premenopausal women); and sex hormone-binding globulin (SHBG) were measured using immunoassays. Levels of free (f) T and E(2) were calculated from absolute concentrations of T, E(2), and SHBG. Odds ratios (ORs) and 95% confidence intervals (CI) were computed using regularized conditional logistic regression. Results: Among premenopausal women, associations with ICC were observed for fT (OR for highest vs. lowest tertile 5.16, 95% CI, 1.50-20.1). SHBG level was associated with a significant downward trend in ICC risk. T, E(2), fE(2), and DHEAS showed nonsignificant positive association with ICC. Progesterone was uninfluential. Among postmenopausal women, associations with ICC were found for T (OR 3.14; 95% CI, 1.21-9.37), whereas E(2) and fT showed nonsignificant positive association. SHBG level was unrelated to ICC risk in postmenopausal women. No associations between any hormone and CIN3 were detected in either pre- or postmenopausal women. Conclusions: Our findings suggest for the first time that T and possibly E(2) may be involved in the etiology of ICC. Impact: The responsiveness of cervical tumors to hormone modulators is worth exploring. Cancer Epidemiol Biomarkers Prev; 20(12); 2532-40. (C) 2011 AACR.

Details

Authors
  • Sabina Rinaldi
  • Martyn Plummer
  • Carine Biessy
  • Xavier Castellsague
  • Kim Overvad
  • Susanne Krueger Kjaer
  • Anne Tjonneland
  • Francoise Clavel-Chapelon
  • Nathalie Chabbert-Buffet
  • Sylvie Mesrine
  • Annekatrin Lukanova
  • Rudolf Kaaks
  • Cornelia Weikert
  • Heiner Boeing
  • Antonia Trichopoulou
  • Pagona Lagiou
  • Dimitrios Trichopoulos
  • Domenico Palli
  • Claudia Agnoli
  • Rosario Tumino
  • Paolo Vineis
  • Salvatore Panico
  • Bas Bueno-de-Mesquita
  • Henk J. van Kranen
  • Petra H. M. Peeters
  • Kjersti Bakken
  • Eiliv Lund
  • Inger Torhild Gram
  • Laudina Rodriguez
  • F. Xavier Bosch
  • Maria-Jose Sanchez
  • Miren Dorronsoro
  • Carmen Navarro
  • Aurelio Barricarte Gurrea
  • Lennart Kjellberg
  • Joakim Dillner
  • Kay-Tee Khaw
  • Nicholas Wareham
  • Naomi E. Allen
  • Ruth Travis
  • Isabelle Romieu
  • Pietro Ferrari
  • Elio Riboli
  • Silvia Franceschi
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)2532-2540
JournalCancer Epidemiology Biomarkers & Prevention
Volume20
Issue number12
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes