Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort.

Abstract

Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet  = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet  = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

• Authors: Renée T Fortner, Jennifer Ose, Melissa A Merritt, Helena Schock, Anne Tjønneland, Louise Hansen, Kim Overvad, Laure Dossus, Françoise Clavel-Chapelon, Laura Baglietto, Heiner Boeing, Antonia Trichopoulou, Vassiliki Benetou, Pagona Lagiou, Claudia Agnoli, Amalia Mattiello, Giovanna Masala, Rosario Tumino, Carlotta Sacerdote, H B As Bueno-de-Mesquita, N Charlotte Onland-Moret, Petra H Peeters, Elisabete Weiderpass, Inger Torhild Gram, Eric J Duell, Nerea Larrañaga, Eva Ardanaz, María-José Sánchez, M-D Chirlaque, Jenny Brändstedt, Annika Idahl, Eva Lundin, Kay-Tee Khaw, Nick Wareham, Ruth C Travis, Sabina Rinaldi, Isabelle Romieu, Marc J Gunter, Elio Riboli, Rudolf Kaaks
• Journal: International journal of cancer (Int J Cancer) Vol. 137 Issue 5 Pg. 1196-208 (Sep 01 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 25656413 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 UICC.

Chemical References

• Contraceptives, Oral, Hormonal

Topics

• Adult
• Aged
• Carcinoma, Ovarian Epithelial
• Contraceptives, Oral, Hormonal (administration & dosage)
• Europe (epidemiology)
• Female
• Humans
• Middle Aged
• Neoplasms, Glandular and Epithelial (epidemiology, pathology, prevention & control)
• Ovarian Neoplasms (epidemiology, pathology, prevention & control)
• Pregnancy
• Prospective Studies
• Risk Factors
• Term Birth