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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

Fortner, Renee T.; Ose, Jennifer; Merritt, Melissa A.; Schock, Helena; Tjonneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Francoise and Baglietto, Laura, et al. (2015) In International Journal of Cancer 137(5). p.1196-1208
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... (More)
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. (Less)
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keywords
ovarian cancer, reproductive factors, histologic subtype, dualistic, model
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International Journal of Cancer
volume
137
issue
5
pages
1196 - 1208
publisher
John Wiley & Sons
external identifiers
  • wos:000356429000020
  • scopus:84931565618
ISSN
0020-7136
DOI
10.1002/ijc.29471
language
English
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yes
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434c0038-5588-44d9-b0d3-c7563539bfa0 (old id 7596553)
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2015-08-03 10:11:06
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@article{434c0038-5588-44d9-b0d3-c7563539bfa0,
  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.},
  author       = {Fortner, Renee T. and Ose, Jennifer and Merritt, Melissa A. and Schock, Helena and Tjonneland, Anne and Hansen, Louise and Overvad, Kim and Dossus, Laure and Clavel-Chapelon, Francoise and Baglietto, Laura and Boeing, Heiner and Trichopoulou, Antonia and Benetou, Vassiliki and Lagiou, Pagona and Agnoli, Claudia and Mattiello, Amalia and Masala, Giovanna and Tumino, Rosario and Sacerdote, Carlotta and Bueno-de-Mesquita, H. B(as) and Onland-Moret, N. Charlotte and Peeters, Petra H. and Weiderpass, Elisabete and Gram, Inger Torhild and Duell, Eric J. and Larranaga, Nerea and Ardanaz, Eva and Sanchez, Maria-Jose and Chirlaque, M-D and Brändstedt, Jenny and Idahl, Annika and Lundin, Eva and Khaw, Kay-Tee and Wareham, Nick and Travis, Ruth C. and Rinaldi, Sabina and Romieu, Isabelle and Gunter, Marc J. and Riboli, Elio and Kaaks, Rudolf},
  issn         = {0020-7136},
  keyword      = {ovarian cancer,reproductive factors,histologic subtype,dualistic,model},
  language     = {eng},
  number       = {5},
  pages        = {1196--1208},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort},
  url          = {http://dx.doi.org/10.1002/ijc.29471},
  volume       = {137},
  year         = {2015},
}