Endogenous sex steroids and risk of cervical carcinoma: results from the EPIC study.
Rinaldi 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 PH., Bakken K., Lund E., Gram IT., Rodríguez L., Bosch FX., Sánchez M-J., Dorronsoro M., Navarro C., Gurrea AB., 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.
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.