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 MJ., Dorronsoro M., Navarro C., Gurrea AB., Kjellberg L., Dillner J., Manjer J., Butt S., Khaw KT., 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.