Endogenous sex steroids and risk of cervical carcinoma: results from the EPIC study.

TitleEndogenous sex steroids and risk of cervical carcinoma: results from the EPIC study.
Publication TypeJournal Article
Year of Publication2011
AuthorsRinaldi S, Plummer M, Biessy C, Castellsagué X, Overvad K, Krüger Kjær S, Tjønneland A, Clavel-Chapelon F, Chabbert-Buffet N, Mesrine S, Lukanova A, Kaaks R, Weikert C, Boeing H, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Agnoli C, Tumino R, Vineis P, Panico S, Bueno-de-Mesquita B, van Kranen HJ, Peeters PHM, Bakken K, Lund E, Gram I T, Rodríguez L, Bosch XF, Sánchez M-J, Dorronsoro M, Navarro C, Gurrea A B, Kjellberg L, Dillner J, Manjer J, Butt S, Khaw K-T, Wareham N, Allen NE, Travis R, Romieu I, Ferrari P, Riboli E, Franceschi S
JournalCancer Epidemiol Biomarkers Prev
Volume20
Issue12
Pagination2532-40
Date Published2011 Dec
ISSN1538-7755
KeywordsAdult, Aged, Case-Control Studies, Estradiol, Europe, Female, Gonadal Steroid Hormones, Humans, Middle Aged, Progesterone, Prospective Studies, Risk Factors, Testosterone, Tumor Markers, Biological, Uterine Cervical Neoplasms
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.

DOI10.1158/1055-9965.EPI-11-0753
Alternate JournalCancer Epidemiol. Biomarkers Prev.
PubMed ID21994406