Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition.
Ose J., Fortner RT., Rinaldi S., Schock H., Overvad K., Tjonneland A., Hansen L., Dossus L., Fournier A., Baglietto L., Romieu I., Kuhn E., Boeing H., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Masala G., Sieri S., Tumino R., Sacerdote C., Mattiello A., Ramon Quiros J., Obón-Santacana M., Larrañaga N., Chirlaque MD., Sánchez MJ., Barricarte A., Peeters PH., Bueno-de-Mesquita HB., Onland-Moret NC., Brändstedt J., Lundin E., Idahl A., Weiderpass E., Gram IT., Lund E., Kaw KT., Travis RC., Merritt MA., Gunther MJ., Riboli E., Kaaks R.
The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.