Article
Author: Brooks, Maria Mori ; Sundfeldt, Karin ; Moysich, Kirsten B ; Rothstein, Joseph H ; Shvetsov, Yurii B ; Hernandez, Brenda Y ; Gronwald, Jacek ; Alsop, Jennifer ; Wang, Chen ; Lycke, Maria ; Beckmann, Matthias W ; Na, Renhua ; Orsulic, Sandra ; Chudecka-Głaz, Anita ; Whittemore, Alice S ; Fereday, Sian ; Goodman, Marc T ; Kelemen, Linda E ; Brand, Alison H ; Steed, Helen ; Taylor, Sarah E ; Murphy, Rachel A ; Longacre, Teri A ; Kluz, Tomasz ; Brenton, James D ; Huntsman, David G ; García, María J ; Winham, Stacey J ; Høgdall, Estrid ; Fasching, Peter A ; Sieh, Weiva ; Modugno, Francesmary ; Cook, Linda S ; Meagher, Nicola S ; Tang, Lu ; Bolithon, Adelyn ; Cybulski, Cezary ; Wentzensen, Nicolas ; Uciński, Jan ; Carney, Michael E ; Wilkens, Lynne R ; Kaznowska, Ewa ; Goode, Ellen L ; Kennedy, Catherine J ; Kjaer, Susanne K ; Fu, Zhuxuan ; Karlan, Beth Y ; Boros, Jessica ; Rodríguez-Antona, Cristina ; Borho, Lauren ; Nevins, Nikilyn ; DeFazio, Anna ; Koziak, Jennifer M ; Samra, Spinder ; Fortner, Renée T ; Bowtell, David D L ; Joseph, Janine M ; Jensen, Allan ; Köbel, Martin ; Pharoah, Paul D P ; McGuire, Valerie ; Antoniou, Antonis C ; Talhouk, Aline ; Songer, Thomas ; Ramus, Susan J ; Webb, Penelope M ; Lester, Jenny ; Hartmann, Arndt ; Jimenez-Linan, Mercedes
OBJECTIVE:Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.
METHOD:We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) between hormonally-linked factors and tumor AR/ER/PR expression using polytomous logistic regression. We assessed survival by AR/ER/PR tumor expression overall and by histotype using Kaplan-Meier curves and Cox proportional hazards models.
RESULTS:Overweight/obesity was associated with higher risk of ER- tumors (OR:1.53, 95 % I:1.18-1.98). Hysterectomy was associated with greater risk of ER+ tumors (OR:4.99, 95 % CI:4.27-5.83), which varied by AR expression (Pheter=0.003). Postmenopause was associated with a higher risk of PR- tumors (OR 1.52, 95 % CI 1.26-1.83), which varied based by AR (Pheter < 0.001) and ER (Pheter < 0.001) expression. Gravidity, oral contraception duration, and breastfeeding duration showed differing dose-response relationships according to AR/ER/PR expression. Hormone therapy use, postmenopause, physical inactivity, and being obese/overweight prior to diagnosis were differentially associated with survival based on AR/ER/PR expression and histotype.
CONCLUSION:EOC has varying risk and prognostic profiles depending on both histotype and AR/ER/PR expression. Biological mechanisms underlying the association between hormonally-linked factors and EOC need to be studied by both histotypes and by AR, ER, and PR expression.