Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

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• 作者：Jennifer Ose ; René ; e T. Fortner ; Sabina Rinaldi ; Helena Schock ; Kim Overvad ; Anne Tjonneland ; Louise Hansen ; Laure Dossus ; Agnes Fournier ; Laura Baglietto ; Isabelle Romieu ; Elisabetta Kuhn ; Heiner Boeing ; Antonia Trichopoulou ; Pagona Lagiou ; Dimitrios Trichopoulos ; Domenico Palli ; Giovanna Masala ; Sabina Sieri ; Rosario Tumino ; Carlotta Sacerdote ; Amalia Mattiello ; Jose Ramon Quiros ; Mireia Obó ; n-Santacana ; Nerea Larrañ ; aga ; Marí ; a-Dolores Chirlaque ; Marí ; a-José ; Sá ; nchez ; Aurelio Barricarte ; Petra H. Peeters ; H. B(as) Bueno-de-Mesquita ; N. Charlotte Onland-Moret ; Jenny Brndstedt ; Eva Lundin ; Annika Idahl ; Elisabete Weiderpass ; Inger T. Gram ; Eiliv Lund ; Kay-Tee Kaw ; Ruth C. Travis ; Melissa A. Merritt ; Marc J. Gunther ; Elio Riboli and Rudolf Kaaks
• 关键词：ovarian carcinoma ; endogenous androgens ; histologic subtype ; androstenedione ; type I tumors ; type II tumors
• 刊名：International Journal of Cancer
• 出版年：2015
• 出版时间：15 January 2015
• 年：2015
• 卷：136
• 期：2
• 页码：399-410
• 全文大小：258K
• ISSN：1097-0215

文摘

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: OR_log2 = 1.99 [0.98–4.06]; high grade: OR_log2 = 0.75 [0.61–0.93], p_het ≤ 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.