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Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk: A Prospective Study in the EPIC Cohort

Lujan-Barroso L 1 , Botteri E 2 , Caini S 3 , Ljungberg B 4 , Roswall N 5 , Tjønneland A 5 Show all authors , Bueno-de-Mesquita B 6 , Gram IT 7 , Tumino R 8 , Kiemeney LA 9 , Liedberg F 10 , Stocks T 11 , Gunter MJ 12 , Murphy N 12 , Cervenka I 13 , Fournier A 13 , Kvaskoff M 13 , Häggström C 14 , Overvad K 15 , Lund E 7 , Waaseth M 16 , Fortner RT 17 , Kühn T 17 , Menéndez V 18 , Sánchez MJ 19 , Santiuste C 20 , Perez-Cornago A 21 , Zamora-Ros R 22 , Cross AJ 23 , Trichopoulou A 24 , Karakatsani A 24 , Peppa E 24 , Palli D 3 , Krogh V 25 , Sciannameo V 26 , Mattiello A 27 , Panico S 27 , van Gils CH 28 , Onland-Moret NC 28 , Barricarte A 20 , Amiano P 20 , Khaw KT 29 , Boeing H 30 , Weiderpass E 12 , Duell EJ 31

Affiliations 

  • 1 Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Gran Via de L'Hospitalet 199-203, L'Hospitalet de Llobregat, Barcelona, Spain. llujan@iconcologia.net
  • 2 Cancer Registry of Norway, Oslo University Hospital, Ullernchausseen 64, Oslo, Norway
  • 3 Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, Florence, Italy
  • 4 Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden
  • 5 Diet, Genes and Environment, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen, Denmark
  • 6 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
  • 7 Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
  • 8 Department of Cancer Registry and Histopathology, "Civic -M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy
  • 9 Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
  • 10 Department of Urology, Skåne University Hospital and Institution of Translational Medicine, Lund University, Jan Waldenströms gata 5, Malmö, Sweden
  • 11 Department of Clinical Sciences Lund, Lund University, Barngatan 4, Lund, Sweden
  • 12 International Agency for Research on Cancer/World Health Organization, Lyon, France
  • 13 Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP) "Health across Generations" Team, Gustave Roussy 114 rue Edouard Vaillant, Villejuif, France
  • 14 Department of Biobank Research, Umeå University, Umeå, Sweden
  • 15 Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
  • 16 Department of Pharmacy, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
  • 17 Division of Cancer Epidemiology, German Cancer Research Center (DFKZ), Im Neuenheimer Feld 280, Heidelberg, Germany
  • 18 Public Health Directorate, C/Ciriaco Miguel Virgil 9, Oviedo, Asturias, Spain
  • 19 Escuela Andaluza de Salud Pública (EASP), Cuesta del Observatorio 4, Granada, Spain
  • 20 Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Av. Monforte de Lemos 3-5, Madrid, Spain
  • 21 Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, Oxford, United Kingdom
  • 22 Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Gran Via de L'Hospitalet 199-203, L'Hospitalet de Llobregat, Barcelona, Spain
  • 23 Faculty of Medicine, Imperial College London, Norfolk Place, London, United Kingdom
  • 24 Hellenic Health Foundation, Kaisareias 13 & Alexandroupoleos, Athens, Greece
  • 25 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumouri, Via Venezian 1, Milano, Italy
  • 26 Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (Turin), Italy
  • 27 Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Via Pansini 5, Naples, Italy
  • 28 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
  • 29 Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom
  • 30 German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114 - 116, Nuthetal, Germany
  • 31 Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Gran Via de L'Hospitalet 199-203, 08908, L'Hospitalet de Llobregat, Barcelona, Spain
Cancer Epidemiol Biomarkers Prev, 2020 Aug;29(8):1654-1664.
PMID: 32467345 DOI: 10.1158/1055-9965.EPI-20-0184

Abstract

BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk.

METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models.

RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25-0.90; P trend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed.

CONCLUSIONS: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk.

IMPACT: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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