Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study

Jelena Bešević¹, Marc J Gunter¹, Renée T Fortner², Konstantinos K Tsilidis^{1

3}, Elisabete Weiderpass^{4

5

6

7}, N Charlotte Onland-Moret⁸, Laure Dossus^{9

10

11}, Anne Tjønneland¹², Louise Hansen¹², Kim Overvad¹³, Sylvie Mesrine^{9

10

11}, Laura Baglietto^{14

15}, Françoise Clavel-Chapelon^{9

10

11}, Rudolf Kaaks², Krasimira Aleksandrova¹⁶, Heiner Boeing¹⁶, Antonia Trichopoulou^{17

18}, Pagona Lagiou^{19

20}, Christina Bamia²⁰, Giovanna Masala²¹, Claudia Agnoli²², Rosario Tumino²³, Fulvio Ricceri^{24

25}, Salvatore Panico²⁶, H Bas Bueno-de-Mesquita^{1

27

28

29}, Petra H Peeters^{1

8}, Mie Jareid⁴, J Ramón Quirós³⁰, Eric J Duell³¹, María-José Sánchez^{32

33}, Nerea Larrañaga^{33

34}, María-Dolores Chirlaque^{33

35}, Aurelio Barricarte^{33

36

37}, Joana A Dias³⁸, Emily Sonestedt³⁸, Annika Idahl^{39

40}, Eva Lundin⁴¹, Nicholas J Wareham⁴², Kay-Tee Khaw⁴³, Ruth C Travis⁴⁴, Sabina Rinaldi⁴⁵, Isabelle Romieu⁴⁵, Elio Riboli¹, Melissa A Merritt¹

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
² Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
³ Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, Ioannina 45110, Greece.
⁴ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø N-9037, Norway.
⁵ Department of Research, Cancer Registry of Norway, PB 5313 Majorstuen, 0304 Oslo, Norway.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, Stockholm 17177, Sweden.
⁷ Genetic Epidemiology Group, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
⁸ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Huispost Str. 6.131, PO Box 85500, Utrecht 3508 GA, The Netherlands.
⁹ Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Lifestyle, Genes and Health: Integrative Trans-generational Epidemiology, Villejuif F-94805, France.
¹⁰ Université Paris Sud, UMRS 1018, Villejuif F-94805, France.
¹¹ Institut Gustave Roussy, Villejuif F-94805, France.
¹² Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen DK-2100, Denmark.
¹³ Section for Epidemiology, Department of Public Health, Aarhus University, Bartholins Alle 2, Aarhus C DK-8000, Denmark.
¹⁴ Cancer Epidemiology Center, Cancer Council of Victoria, 615 St Kilda Road, Melbourne 3004, Victoria, Australia.
¹⁵ Center for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne 3010, Victoria, Australia.
¹⁶ Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, Nuthetal 14558, Germany.
¹⁷ Hellenic Health Foundation, 13 Kaisareias Street, Athens GR-115 27, Greece.
¹⁸ Bureau of Epidemiologic Research, Academy of Athens, 23 Alexandroupoleos Street, Athens GR-115 27, Greece.
¹⁹ Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
²⁰ Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Mikras Asias 75, Goudi, Athens GR-115 27, Greece.
²¹ Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Ponte Nuovo Palazzina 28A 'Mario Fiori', Via delle Oblate 4, Florence 50141, Italy.
²² Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, Milano 20133, Italy.
²³ Cancer Registry and Histopathology Unit, 'Civic-M.P. Arezzo' Hospital, ASP, Via Dante No. 109, Ragusa 97100, Italy.
²⁴ Unit of Epidemiology, Regional Health Service ASL TO3, Via Sabaudia 164, Grugliasco (TO) 10095, Italy.
²⁵ Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Via Santena 7, Turin 10126, Italy.
²⁶ Dipartimento di Medicina Clinica e Chirurgia, Federico II University, via Pansini 5, 80131 Naples, Italy.
²⁷ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven 3720 BA, The Netherlands.
²⁸ Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Heidelberglann 100, Utrecht 3584 cx, The Netherlands.
²⁹ Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
³⁰ Public Health Directorate, Asturias, Ciriaco Miguel Vigil St 9, Oviedo 33006, Spain.
³¹ Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Avda Gran Via 199-203, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
³² Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, Hospitales Universitarios de Granada/Universidad de Granada, Cuesta del Observatorio, 4, Campus Universitario de Cartuja, Granada 18080, Spain.
³³ CIBER de Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, Madrid 28029, Spain.
³⁴ Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Donostia, Spain.
³⁵ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Ronda de Levante 11, Murcia 30008, Spain.
³⁶ Navarra Public Health Institute, c/Leyre 15, Pamplona 31003, Spain.
³⁷ IdiSNA, Navarra Institute for Health Research, Recinto de Complejo Hospitalario de Navarra c/Irunlarrea 3, Pamplona 31008, Spain.
³⁸ Department of Clinical Sciences Malmö, Lund University, Malmö 20502, Sweden.
³⁹ Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, SE-901 87 Umeå, Sweden.
⁴⁰ Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, SE-901 87 Umeå, Sweden.
⁴¹ Department of Medical Biosciences and Pathology, Umeå University, Umeå SE-901 87, Sweden.
⁴² MRC Epidemiology Unit, University of Cambridge, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
⁴³ School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Rd, Cambridge CB2 0SP, UK.
⁴⁴ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Oxford OX3 7LF, UK.
⁴⁵ International Agency for Research on Cancer, 150 Cours Albert-Thomas, Lyon Cedex 08 69372, France.

PMID: 26554655
PMCID: PMC4705888
DOI: 10.1038/bjc.2015.377

Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study

Jelena Bešević et al. Br J Cancer. 2015.

. 2015 Dec 1;113(11):1622-31.

doi: 10.1038/bjc.2015.377. Epub 2015 Nov 10.

Authors

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
² Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
³ Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, Ioannina 45110, Greece.
⁴ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø N-9037, Norway.
⁵ Department of Research, Cancer Registry of Norway, PB 5313 Majorstuen, 0304 Oslo, Norway.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, Stockholm 17177, Sweden.
⁷ Genetic Epidemiology Group, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
⁸ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Huispost Str. 6.131, PO Box 85500, Utrecht 3508 GA, The Netherlands.
⁹ Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Lifestyle, Genes and Health: Integrative Trans-generational Epidemiology, Villejuif F-94805, France.
¹⁰ Université Paris Sud, UMRS 1018, Villejuif F-94805, France.
¹¹ Institut Gustave Roussy, Villejuif F-94805, France.
¹² Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen DK-2100, Denmark.
¹³ Section for Epidemiology, Department of Public Health, Aarhus University, Bartholins Alle 2, Aarhus C DK-8000, Denmark.
¹⁴ Cancer Epidemiology Center, Cancer Council of Victoria, 615 St Kilda Road, Melbourne 3004, Victoria, Australia.
¹⁵ Center for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne 3010, Victoria, Australia.
¹⁶ Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, Nuthetal 14558, Germany.
¹⁷ Hellenic Health Foundation, 13 Kaisareias Street, Athens GR-115 27, Greece.
¹⁸ Bureau of Epidemiologic Research, Academy of Athens, 23 Alexandroupoleos Street, Athens GR-115 27, Greece.
¹⁹ Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
²⁰ Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Mikras Asias 75, Goudi, Athens GR-115 27, Greece.
²¹ Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Ponte Nuovo Palazzina 28A 'Mario Fiori', Via delle Oblate 4, Florence 50141, Italy.
²² Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, Milano 20133, Italy.
²³ Cancer Registry and Histopathology Unit, 'Civic-M.P. Arezzo' Hospital, ASP, Via Dante No. 109, Ragusa 97100, Italy.
²⁴ Unit of Epidemiology, Regional Health Service ASL TO3, Via Sabaudia 164, Grugliasco (TO) 10095, Italy.
²⁵ Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Via Santena 7, Turin 10126, Italy.
²⁶ Dipartimento di Medicina Clinica e Chirurgia, Federico II University, via Pansini 5, 80131 Naples, Italy.
²⁷ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven 3720 BA, The Netherlands.
²⁸ Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Heidelberglann 100, Utrecht 3584 cx, The Netherlands.
²⁹ Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
³⁰ Public Health Directorate, Asturias, Ciriaco Miguel Vigil St 9, Oviedo 33006, Spain.
³¹ Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Avda Gran Via 199-203, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
³² Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, Hospitales Universitarios de Granada/Universidad de Granada, Cuesta del Observatorio, 4, Campus Universitario de Cartuja, Granada 18080, Spain.
³³ CIBER de Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, Madrid 28029, Spain.
³⁴ Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Donostia, Spain.
³⁵ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Ronda de Levante 11, Murcia 30008, Spain.
³⁶ Navarra Public Health Institute, c/Leyre 15, Pamplona 31003, Spain.
³⁷ IdiSNA, Navarra Institute for Health Research, Recinto de Complejo Hospitalario de Navarra c/Irunlarrea 3, Pamplona 31008, Spain.
³⁸ Department of Clinical Sciences Malmö, Lund University, Malmö 20502, Sweden.
³⁹ Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, SE-901 87 Umeå, Sweden.
⁴⁰ Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, SE-901 87 Umeå, Sweden.
⁴¹ Department of Medical Biosciences and Pathology, Umeå University, Umeå SE-901 87, Sweden.
⁴² MRC Epidemiology Unit, University of Cambridge, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
⁴³ School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Rd, Cambridge CB2 0SP, UK.
⁴⁴ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Oxford OX3 7LF, UK.
⁴⁵ International Agency for Research on Cancer, 150 Cours Albert-Thomas, Lyon Cedex 08 69372, France.

PMID: 26554655
PMCID: PMC4705888
DOI: 10.1038/bjc.2015.377

Abstract

Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521,330 total participants (approximately 370,000 women) aged 25-70 years at recruitment from 1992 to 2000.

Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre.

Results: After a mean follow-up of 3.6 years (±3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR=0.80, 95% CI=0.62-1.03) and a significant survival benefit in long-term MHT users (⩾5 years use vs never use, HR=0.70, 95% CI=0.50-0.99, P(trend)=0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk.

Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.

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References

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Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study

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Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study

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