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

Rinaldi, Sabina; Plummer, Martyn; Biessy, Carine; Castellsague, Xavier; Overvad, Kim; Kjaer, Susanne Krueger; Tjonneland, Anne; Clavel-Chapelon, Francoise; Chabbert-Buffet, Nathalie and Mesrine, Sylvie, et al. (2011) In Cancer Epidemiology Biomarkers & Prevention 20(12). p.2532-2540
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... (More)
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. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
20
issue
12
pages
2532 - 2540
publisher
American Association for Cancer Research
external identifiers
  • wos:000298234900009
  • scopus:83055198317
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-11-0753
language
English
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6a7636a4-a80f-4d8b-a84b-5771d26747ba (old id 2333245)
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2012-02-01 07:38:11
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@article{6a7636a4-a80f-4d8b-a84b-5771d26747ba,
  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.},
  author       = {Rinaldi, Sabina and Plummer, Martyn and Biessy, Carine and Castellsague, Xavier and Overvad, Kim and Kjaer, Susanne Krueger and Tjonneland, Anne and Clavel-Chapelon, Francoise and Chabbert-Buffet, Nathalie and Mesrine, Sylvie and Lukanova, Annekatrin and Kaaks, Rudolf and Weikert, Cornelia and Boeing, Heiner and Trichopoulou, Antonia and Lagiou, Pagona and Trichopoulos, Dimitrios and Palli, Domenico and Agnoli, Claudia and Tumino, Rosario and Vineis, Paolo and Panico, Salvatore and Bueno-de-Mesquita, Bas and van Kranen, Henk J. and Peeters, Petra H. M. and Bakken, Kjersti and Lund, Eiliv and Gram, Inger Torhild and Rodriguez, Laudina and Bosch, F. Xavier and Sanchez, Maria-Jose and Dorronsoro, Miren and Navarro, Carmen and Barricarte Gurrea, Aurelio and Kjellberg, Lennart and Dillner, Joakim and Manjer, Jonas and Butt, Salma and Khaw, Kay-Tee and Wareham, Nicholas and Allen, Naomi E. and Travis, Ruth and Romieu, Isabelle and Ferrari, Pietro and Riboli, Elio and Franceschi, Silvia},
  issn         = {1538-7755},
  language     = {eng},
  number       = {12},
  pages        = {2532--2540},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Endogenous Sex Steroids and Risk of Cervical Carcinoma: Results from the EPIC Study},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-11-0753},
  volume       = {20},
  year         = {2011},
}