Multicenter Study

. 2015 Sep 1;137(5):1196-208.

doi: 10.1002/ijc.29471. Epub 2015 Feb 26.

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

Renée T Fortner¹, Jennifer Ose¹, Melissa A Merritt², Helena Schock¹, Anne Tjønneland³, Louise Hansen³, Kim Overvad⁴, Laure Dossus^{5

6

7}, Françoise Clavel-Chapelon^{5

6

7}, Laura Baglietto^{8

9}, Heiner Boeing¹⁰, Antonia Trichopoulou^{11

12

13}, Vassiliki Benetou¹³, Pagona Lagiou^{12

13

14}, Claudia Agnoli¹⁵, Amalia Mattiello¹⁶, Giovanna Masala¹⁷, Rosario Tumino¹⁸, Carlotta Sacerdote¹⁹, H B As Bueno-de-Mesquita^{2

20

21

22}, N Charlotte Onland-Moret²³, Petra H Peeters²³, Elisabete Weiderpass^{24

25

26

27}, Inger Torhild Gram²⁴, Eric J Duell²⁸, Nerea Larrañaga^{29

30}, Eva Ardanaz^{30

31}, María-José Sánchez^{30

32}, M-D Chirlaque^{30

33}, Jenny Brändstedt^{34

35}, Annika Idahl^{36

37}, Eva Lundin^{38

39}, Kay-Tee Khaw⁴⁰, Nick Wareham⁴¹, Ruth C Travis⁴², Sabina Rinaldi⁴³, Isabelle Romieu⁴³, Marc J Gunter², Elio Riboli², Rudolf Kaaks¹

Affiliations

¹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
³ Danish Cancer Society Research Center, Copenhagen, Denmark.
⁴ Department of Public Health Aarhus University, Section for Epidemiology, Aarhus, Denmark.
⁵ U1018, Nutrition, Hormones and Women's Health Team, Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.
⁶ Université Paris Sud, Unité Mixte de Recherche Scientifique 1018, Villejuif, France.
⁷ U1018, Nutrition, Hormones and Women's Health Team, Institut Gustave Roussy, Villejuif, France.
⁸ Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia.
⁹ Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Australia.
¹⁰ Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany.
¹¹ Hellenic Health Foundation, Athens, Greece.
¹² Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
¹³ Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
¹⁴ Department of Epidemiology, Harvard School of Public Health, Boston, MA.
¹⁵ Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
¹⁶ Dipartimento Di Medicina Clinica E Chirurgia, Federco II University, Naples, Italy.
¹⁷ Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
¹⁸ Cancer Registry and Histopathology Unit, "Civic-M.P. Arezzo" Hospita, Ragusa, Italy.
¹⁹ Unit of Cancer Epidemiology, AO Citta' Della Salute E Della Scienza-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy.
²⁰ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
²¹ Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
²² Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
²³ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, Epidemiology, University Medical Center Utrecht, Utrecht, The Netherlands.
²⁴ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, the Arctic University of Norway, Tromsø, Norway.
²⁵ Cancer Registry of Norway, Oslo, Norway.
²⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁷ Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
²⁸ Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
²⁹ Basque Health Department, Public Health Division of Gipuzkoa, BIODonostia Research Institute, Donostia-San Sebastián, Spain.
³⁰ CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
³¹ Epidemiology Unit, Navarre Public Health Institute, Pamplona, Spain.
³² Escuela Andaluza De Salud Pública, Instituto De Investigación Biosanitaria Ibs.GRANADA. Hospitales Universitarios De Granada/Universidad De Granada, Granada, Spain.
³³ Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
³⁴ Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
³⁵ Department of Surgery, Skåne University Hospital, Malmö, Sweden.
³⁶ Department of Clinical Sciences, Obstetrics and Gynecology, Nutritional Research Umeå University, Umeå, Sweden.
³⁷ Department of Public Health and Clinical Medicine, Nutritional Research Umeå University, Umeå, Sweden.
³⁸ Department of Medical Biosciences, University of Umeå, Umeå, Sweden.
³⁹ Department of Public Health and Clinical Medicine, University of Umeå, Umeå, Sweden.
⁴⁰ Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
⁴¹ MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
⁴² Cancer Epidemiology Unit, University of Oxford, Oxford, OX30NR, United Kingdom.
⁴³ Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.

PMID: 25656413
PMCID: PMC6284794
DOI: 10.1002/ijc.29471

Multicenter Study

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

Renée T Fortner et al. Int J Cancer. 2015.

. 2015 Sep 1;137(5):1196-208.

doi: 10.1002/ijc.29471. Epub 2015 Feb 26.

Authors

Affiliations

¹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
³ Danish Cancer Society Research Center, Copenhagen, Denmark.
⁴ Department of Public Health Aarhus University, Section for Epidemiology, Aarhus, Denmark.
⁵ U1018, Nutrition, Hormones and Women's Health Team, Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.
⁶ Université Paris Sud, Unité Mixte de Recherche Scientifique 1018, Villejuif, France.
⁷ U1018, Nutrition, Hormones and Women's Health Team, Institut Gustave Roussy, Villejuif, France.
⁸ Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia.
⁹ Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Australia.
¹⁰ Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany.
¹¹ Hellenic Health Foundation, Athens, Greece.
¹² Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
¹³ Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
¹⁴ Department of Epidemiology, Harvard School of Public Health, Boston, MA.
¹⁵ Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
¹⁶ Dipartimento Di Medicina Clinica E Chirurgia, Federco II University, Naples, Italy.
¹⁷ Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
¹⁸ Cancer Registry and Histopathology Unit, "Civic-M.P. Arezzo" Hospita, Ragusa, Italy.
¹⁹ Unit of Cancer Epidemiology, AO Citta' Della Salute E Della Scienza-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy.
²⁰ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
²¹ Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
²² Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
²³ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, Epidemiology, University Medical Center Utrecht, Utrecht, The Netherlands.
²⁴ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, the Arctic University of Norway, Tromsø, Norway.
²⁵ Cancer Registry of Norway, Oslo, Norway.
²⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁷ Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
²⁸ Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
²⁹ Basque Health Department, Public Health Division of Gipuzkoa, BIODonostia Research Institute, Donostia-San Sebastián, Spain.
³⁰ CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
³¹ Epidemiology Unit, Navarre Public Health Institute, Pamplona, Spain.
³² Escuela Andaluza De Salud Pública, Instituto De Investigación Biosanitaria Ibs.GRANADA. Hospitales Universitarios De Granada/Universidad De Granada, Granada, Spain.
³³ Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
³⁴ Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
³⁵ Department of Surgery, Skåne University Hospital, Malmö, Sweden.
³⁶ Department of Clinical Sciences, Obstetrics and Gynecology, Nutritional Research Umeå University, Umeå, Sweden.
³⁷ Department of Public Health and Clinical Medicine, Nutritional Research Umeå University, Umeå, Sweden.
³⁸ Department of Medical Biosciences, University of Umeå, Umeå, Sweden.
³⁹ Department of Public Health and Clinical Medicine, University of Umeå, Umeå, Sweden.
⁴⁰ Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
⁴¹ MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
⁴² Cancer Epidemiology Unit, University of Oxford, Oxford, OX30NR, United Kingdom.
⁴³ Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.

PMID: 25656413
PMCID: PMC6284794
DOI: 10.1002/ijc.29471

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.

Keywords: dualistic model; histologic subtype; ovarian cancer; reproductive factors.

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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

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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

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