Menstrual factors, reproductive history, hormone use, and Urothelial carcinoma risk: A prospective study in the EPIC cohort

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  • Leila Lujan-Barroso, Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Spanien
  • Edoardo Botteri, Norwegian University of Science and Technology, Trondheim, Norway; Colorectal Cancer Registry, Cancer Registry of Norway, Oslo, Norway(m)., Norge
  • Saverio Caini, Institute for Cancer Research, Italien
  • Borje Ljungberg, Umea University Hospital., Sverige
  • Nina Roswall, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark., Danmark
  • Anne Tjonneland, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark., Danmark
  • Bas Bueno-de-Mesquita, National Institute for Public Health and the Environment (RIVM), Holland
  • Inger T Gram, University of Tromsø, Tromsø, Norge
  • Rosario Tumino, Cancer Registry and Histopathology Department, 'Civic - M.P.Arezzo' Hospital, Italy., Italien
  • Lambertus A Kiemeney, Radboud University Nijmegen Medical Centre, Holland
  • Fredrik Liedberg, Skåne University Hospital, Lund, Sverige
  • Tanja Stocks, Department of Nephrology in Lund, Clinical Sciences Lund, Skåne University Hospital and Lund University, Lund, Sweden., Sverige
  • Marc J Gunter, European Society for enteral and parenteral Nutrition and Metabolism., International Agency for Research on Cancer
  • ,
  • Neil Murphy, International Agency for Research on Cancer, Frankrig
  • Iris Cervenka, Nutrition, Hormones and Women's Health Team, INSERM, CESP Centre for Research in Epidemiology and Population Health, U1018, Univ Paris Sud., Frankrig
  • Agnes Fournier, Univ Paris 11, University of Paris Sud - Paris XI, Lab Geosci Paris Sud GEOPS, UMR 8148, Frankrig
  • Marina Kvaskoff, Inst Gustave Roussy, Gustave Roussy, UNICANCER, Frankrig
  • Christel Häggström, Uppsala University, Sverige
  • Kim Overvad
  • Eiliv Lund, University of Tromsø, Tromsø, Norge
  • Marit Waaseth, University of Tromsø, Tromsø, Norge
  • Renée Turzanski Fortner, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Tyskland
  • Tilman Kühn, German Cancer Research Center, Tyskland
  • Virginia Menéndez, Public Health Directorate
  • ,
  • Maria-Jose Sánchez, Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain., Spanien
  • Carmen Santiuste, Murcia Regional Health Council, Murcia, Spain., Spanien
  • Aurora Perez-Cornago, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom; Department of Physics, University of Oxford, Oxford, United Kingdom; University of Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Storbritannien
  • Raul Zamora-Ros, Bellvitge Biomedical Research Institute, Spanien
  • Amanda J Cross, Imperial Coll London, Imperial College London, UKDRI, Storbritannien
  • Antonia Trichopoulou, Hellenic Health Foundation., Grækenland
  • Anna Karakatsani, National and Kapodistrian University of Athens, Grækenland
  • Eleni Peppa, Hellenic Health Foundation., Grækenland
  • Domenico Palli, Institute for Cancer Research
  • ,
  • Vittorio Krogh, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori., Italien
  • Veronica Sciannameo, Regional Health Service
  • ,
  • Amalia Mattiello, Federico II University Hospital, Italien
  • Salvatore Panico, Federico II University Hospital
  • ,
  • Carla H van Gils, Department of Otorhinolaryngology and Head & Neck Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:, Holland
  • N Charlotte Onland-Moret, Univ Utrecht, Utrecht University Medical Center, Utrecht University, Univ Med Ctr Utrecht, Regenerat Med Ctr, Holland
  • Aurelio Barricarte, CIBER Epidemiologia y Salud Publica (CIBERESP)., Spanien
  • Pilar Amiano, Biodonostia Health Research Institute
  • ,
  • Kay-Tee Khaw, Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom; Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom;, Storbritannien
  • Heiner Boeing, German Institute of Human Nutrition Potsdam-Rehbruecke, Tyskland
  • Elisabete Weiderpass, International Agency for Research on Cancer, Frankrig
  • Eric J Duell, Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO IDIBELL)., Spanien

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

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

RESULTS: During a mean of 15 years of follow-up, 529 women developed UC. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with UC risk (HR≥5vs1=0.48, 0.25-0.90; P-trend in parous women=0.010) and MHT-use (compared to non-use) was positively associated with UC 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 UC risk was observed. Association between MHT-use and UC risk only remained significant in current-smokers. No heterogeneity of the risk estimations in the final model was observed by tumour aggressiveness or by tumour grade. A positive association between the MTH-use and non-muscle invasive UC risk was observed.

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

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

TidsskriftCancer Epidemiology, Biomarkers & Prevention
Sider (fra-til)1654-1664
Antal sider11
StatusUdgivet - aug. 2020

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Copyright ©2020, American Association for Cancer Research.

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