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Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

Ose, Jennifer; Fortner, Renee T.; Rinaldi, Sabina; Schock, Helena; Overvad, Kim; Tjonneland, Anne; Hansen, Louise; Dossus, Laure; Fournier, Agnes and Baglietto, Laura, et al. (2014) In International Journal of Cancer 136(2). p.399-410
Abstract
The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible... (More)
The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2=0.79, 95% confidence interval [CI]=[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2=1.99 [0.98-4.06]; high grade: ORlog2=0.75 [0.61-0.93], p(het)0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. What's new? There appear to be several types of epithelial invasive ovarian cancer (EOC), and hormone-related risk factors are poorly understood. In this study, the authors found that the impact of endogenous androgens on the risk of developing EOC differed depending upon tumor characteristics. Androgen concentrations were positively associated with the risk of low-grade and type-I carcinomas, but the study found an inverse association for high-grade tumors. These findings support a possible role for androgens in ovarian carcinogenesis, and emphasize the need for additional research. (Less)
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keywords
ovarian carcinoma, endogenous androgens, histologic subtype, androstenedione, type I tumors, type II tumors
in
International Journal of Cancer
volume
136
issue
2
pages
399 - 410
publisher
John Wiley & Sons
external identifiers
  • wos:000344596600018
  • scopus:84922290714
ISSN
0020-7136
DOI
10.1002/ijc.29000
language
English
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@article{8a4061fe-01bb-4af7-be44-fe815be80166,
  abstract     = {The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2=0.79, 95% confidence interval [CI]=[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2=1.99 [0.98-4.06]; high grade: ORlog2=0.75 [0.61-0.93], p(het)0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. What's new? There appear to be several types of epithelial invasive ovarian cancer (EOC), and hormone-related risk factors are poorly understood. In this study, the authors found that the impact of endogenous androgens on the risk of developing EOC differed depending upon tumor characteristics. Androgen concentrations were positively associated with the risk of low-grade and type-I carcinomas, but the study found an inverse association for high-grade tumors. These findings support a possible role for androgens in ovarian carcinogenesis, and emphasize the need for additional research.},
  author       = {Ose, Jennifer and Fortner, Renee T. and Rinaldi, Sabina and Schock, Helena and Overvad, Kim and Tjonneland, Anne and Hansen, Louise and Dossus, Laure and Fournier, Agnes and Baglietto, Laura and Romieu, Isabelle and Kuhn, Elisabetta and Boeing, Heiner and Trichopoulou, Antonia and Lagiou, Pagona and Trichopoulos, Dimitrios and Palli, Domenico and Masala, Giovanna and Sieri, Sabina and Tumino, Rosario and Sacerdote, Carlotta and Mattiello, Amalia and Ramon Quiros, Jose and Obon-Santacana, Mireia and Larranaga, Nerea and Chirlaque, Maria-Dolores and Sanchez, Maria-Jose and Barricarte, Aurelio and Peeters, Petra H. and Bueno-de-Mesquita, H. B(as) and Onland-Moret, N. Charlotte and Brändstedt, Jenny and Lundin, Eva and Idahl, Annika and Weiderpass, Elisabete and Gram, Inger T. and Lund, Eiliv and Kaw, Kay-Tee and Travis, Ruth C. and Merritt, Melissa A. and Gunther, Marc J. and Riboli, Elio and Kaaks, Rudolf},
  issn         = {0020-7136},
  keyword      = {ovarian carcinoma,endogenous androgens,histologic subtype,androstenedione,type I tumors,type II tumors},
  language     = {eng},
  number       = {2},
  pages        = {399--410},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition},
  url          = {http://dx.doi.org/10.1002/ijc.29000},
  volume       = {136},
  year         = {2014},
}