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Reproductive and hormone‐related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort
Author(s) -
Fortner Renée T.,
Ose Jennifer,
Merritt Melissa A.,
Schock Helena,
Tjønneland Anne,
Hansen Louise,
Overvad Kim,
Dossus Laure,
ClavelChapelon Françoise,
Baglietto Laura,
Boeing Heiner,
Trichopoulou Antonia,
Benetou Vassiliki,
Lagiou Pagona,
Agnoli Claudia,
Mattiello Amalia,
Masala Giovanna,
Tumino Rosario,
Sacerdote Carlotta,
BuenodeMesquita H.Bas,
OnlandMoret N. Charlotte,
Peeters Petra H.,
Weiderpass Elisabete,
Torhild Gram Inger,
Duell Eric J,
Larrañaga Nerea,
Ardanaz Eva,
Sánchez MaríaJosé,
Chirlaque MD,
Brändstedt Jenny,
Idahl Annika,
Lundin Eva,
Khaw KayTee,
Wareham Nick,
Travis Ruth C.,
Rinaldi Sabina,
Romieu Isabelle,
Gunter Marc J.,
Riboli Elio,
Kaaks Rudolf
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29471
Subject(s) - serous fluid , medicine , clear cell , pregnancy , relative risk , oncology , histology , risk factor , cancer , prospective cohort study , cohort study , gynecology , pathology , confidence interval , immunohistochemistry , biology , genetics
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.