title: Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition.
abstract: 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.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Jennifer
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authors.forename: Renée T
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authors.forename: Laure
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authors.forename: Agnes
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authors.lastname: Baglietto
authors.forename: Isabelle
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authors.forename: Elisabetta
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authors.lastname: Kuhn
authors.forename: Heiner
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authors.forename: Antonia
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authors.lastname: Trichopoulou
authors.forename: Pagona
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authors.forename: Rosario
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authors.forename: Jose
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authors.lastname: Ramon Quiros
authors.forename: Mireia
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authors.lastname: Obón-Santacana
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authors.lastname: Larrañaga
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Jenny
authors.initials: J
authors.lastname: Brändstedt
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
authors.forename: Annika
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authors.lastname: Idahl
authors.forename: Elisabete
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authors.lastname: Weiderpass
authors.forename: Inger T
authors.initials: IT
authors.lastname: Gram
authors.forename: Eiliv
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authors.lastname: Lund
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Kaw
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Merritt
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunther
authors.forename: Elio
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authors.lastname: Riboli
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D005060:Europe / Q000453:epidemiology; D005185:Fallopian Tube Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D009752:Nutritional Status; D010051:Ovarian Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
chemical_list: D000728:Androgens; D012738:Sex Hormone-Binding Globulin
keywords: androstenedione; endogenous androgens; histologic subtype; ovarian carcinoma; type I tumors; type II tumors