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

Journal article

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.

Authors: Rinaldi, S; Plummer, M; Biessy, C; Castellsagué, X; Overvad, K

• Publication status: Published
• Journal: Cancer epidemiology, biomarkers and prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• Volume: 20
• Issue: 12
• Pages: 2532-2540
• Publication date: 2011-12-01
• DOI: 10.1158/1055-9965.epi-11-0753
• EISSN: 1538-7755
• ISSN: 1055-9965
• Language: English
• Keywords: Female; Humans; Uterine Cervical Neoplasms; Prospective Studies; Europe; Gonadal Steroid Hormones; Estradiol; Tumor Markers, Biological; Testosterone; Risk Factors; Middle Aged; Adult; Aged; Case-Control Studies; Progesterone