title: Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort.
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.
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Renée T
authors: RT
authors: Fortner
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Jennifer
authors: J
authors: Ose
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Melissa A
authors: MA
authors: Merritt
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Helena
authors: H
authors: Schock
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Anne
authors: A
authors: Tjønneland
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Louise
authors: L
authors: Hansen
authors: Department of Public Health Aarhus University, Section for Epidemiology, Aarhus, Denmark.
authors: Kim
authors: K
authors: Overvad
authors: U1018, Nutrition, Hormones and Women's Health Team, Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.|Université Paris Sud, Unité Mixte de Recherche Scientifique 1018, Villejuif, France.|U1018, Nutrition, Hormones and Women's Health Team, Institut Gustave Roussy, Villejuif, France.
authors: Laure
authors: L
authors: Dossus
authors: U1018, Nutrition, Hormones and Women's Health Team, Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.|Université Paris Sud, Unité Mixte de Recherche Scientifique 1018, Villejuif, France.|U1018, Nutrition, Hormones and Women's Health Team, Institut Gustave Roussy, Villejuif, France.
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia.|Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Australia.
authors: Laura
authors: L
authors: Baglietto
authors: Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany.
authors: Heiner
authors: H
authors: Boeing
authors: Hellenic Health Foundation, Athens, Greece.|Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.|Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors: Antonia
authors: A
authors: Trichopoulou
authors: Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors: Vassiliki
authors: V
authors: Benetou
authors: Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.|Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.|Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors: Pagona
authors: P
authors: Lagiou
authors: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
authors: Claudia
authors: C
authors: Agnoli
authors: Dipartimento Di Medicina Clinica E Chirurgia, Federco II University, Naples, Italy.
authors: Amalia
authors: A
authors: Mattiello
authors: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
authors: Giovanna
authors: G
authors: Masala
authors: Cancer Registry and Histopathology Unit, "Civic-M.P. Arezzo" Hospita, Ragusa, Italy.
authors: Rosario
authors: R
authors: Tumino
authors: Unit of Cancer Epidemiology, AO Citta' Della Salute E Della Scienza-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy.
authors: Carlotta
authors: C
authors: Sacerdote
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.|Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.|Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: H B As
authors: HB
authors: Bueno-de-Mesquita
authors: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, Epidemiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: N Charlotte
authors: NC
authors: Onland-Moret
authors: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, Epidemiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Petra H
authors: PH
authors: Peeters
authors: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, the Arctic University of Norway, Tromsø, Norway.|Cancer Registry of Norway, Oslo, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
authors: Elisabete
authors: E
authors: Weiderpass
authors: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, the Arctic University of Norway, Tromsø, Norway.
authors: Inger
authors: I
authors: Torhild Gram
authors: Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
authors: Eric J
authors: EJ
authors: Duell
authors: Basque Health Department, Public Health Division of Gipuzkoa, BIODonostia Research Institute, Donostia-San Sebastián, Spain.|CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors: Nerea
authors: N
authors: Larrañaga
authors: CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.|Epidemiology Unit, Navarre Public Health Institute, Pamplona, Spain.
authors: Eva
authors: E
authors: Ardanaz
authors: CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.|Escuela Andaluza De Salud Pública, Instituto De Investigación Biosanitaria Ibs.GRANADA. Hospitales Universitarios De Granada/Universidad De Granada, Granada, Spain.
authors: María-José
authors: MJ
authors: Sánchez
authors: CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.|Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
authors: M-D
authors: MD
authors: Chirlaque
authors: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.|Department of Surgery, Skåne University Hospital, Malmö, Sweden.
authors: Jenny
authors: J
authors: Brändstedt
authors: Department of Clinical Sciences, Obstetrics and Gynecology, Nutritional Research Umeå University, Umeå, Sweden.|Department of Public Health and Clinical Medicine, Nutritional Research Umeå University, Umeå, Sweden.
authors: Annika
authors: A
authors: Idahl
authors: Department of Medical Biosciences, University of Umeå, Umeå, Sweden.|Department of Public Health and Clinical Medicine, University of Umeå, Umeå, Sweden.
authors: Eva
authors: E
authors: Lundin
authors: Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
authors: Kay-Tee
authors: KT
authors: Khaw
authors: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors: Nick
authors: N
authors: Wareham
authors: Cancer Epidemiology Unit, University of Oxford, Oxford, OX30NR, United Kingdom.
authors: Ruth C
authors: RC
authors: Travis
authors: Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
authors: Sabina
authors: S
authors: Rinaldi
authors: Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
authors: Isabelle
authors: I
authors: Romieu
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Marc J
authors: MJ
authors: Gunter
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Elio
authors: E
authors: Riboli
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Rudolf
authors: R
authors: Kaaks
mesh_terms: D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control*; D011247:Pregnancy; D011446:Prospective Studies; D012307:Risk Factors; D047929:Term Birth
chemical_list: D003278:Contraceptives, Oral, Hormonal
keywords: dualistic model; histologic subtype; ovarian cancer; reproductive factors
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