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

Research output: Contribution to journalArticle

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 (p(het)=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]; p(het)=0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes. What's new? Reproductive and hormone-related risk factors for epithelial ovarian cancer (EOC) have been extensively investigated. However, EOC is increasingly recognized as a heterogeneous disease and risk factor differences across EOC subtypes, as defined by the recently proposed dualistic pathway of ovarian carcinogenesis and histological characteristics, are not well understood. Here, the authors present a detailed prospective investigation on reproductive and hormone-related risk factors for borderline tumors and epithelial ovarian cancer by main histological subtypes and, for the first time, by the types defined by the dualistic pathway. The results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

Details

Authors
  • Renee T. Fortner
  • Jennifer Ose
  • Melissa A. Merritt
  • Helena Schock
  • Anne Tjonneland
  • Louise Hansen
  • Kim Overvad
  • Laure Dossus
  • Francoise 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 Larranaga
  • Eva Ardanaz
  • Maria-Jose Sanchez
  • M-D Chirlaque
  • Annika Idahl
  • Eva Lundin
  • Kay-Tee Khaw
  • Nick Wareham
  • Ruth C. Travis
  • Sabina Rinaldi
  • Isabelle Romieu
  • Marc J. Gunter
  • Elio Riboli
  • Rudolf Kaaks
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • ovarian cancer, reproductive factors, histologic subtype, dualistic, model
Original languageEnglish
Pages (from-to)1196-1208
JournalInternational Journal of Cancer
Volume137
Issue number5
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000)