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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Leila Lujan-Barroso
  • Edoardo Botteri
  • Saverio Caini
  • Boerje Ljungberg
  • Nina Roswall
  • Bas Bueno-de-Mesquita
  • Inger T. Gram
  • Rosario Tumino
  • Lambertus A. Kiemeney
  • Fredrik Liedberg
  • Tanja Stocks
  • Marc J. Gunter
  • Neil Murphy
  • Iris Cervenka
  • Agnes Fournier
  • Marina Kvaskoff
  • Christel Haeggstroem
  • Kim Overvad
  • Eiliv Lund
  • Marit Waaseth
  • Renee Turzanski Fortner
  • Tilman Kuhn
  • Virginia Menendez
  • Maria-Jose Sanchez
  • Carmen Santiuste
  • Aurora Perez-Cornago
  • Raul Zamora-Ros
  • Amanda J. Cross
  • Antonia Trichopoulou
  • Anna Karakatsani
  • Eleni Peppa
  • Domenico Palli
  • Vittorio Krogh
  • Veronica Sciannameo
  • Amalia Mattiello
  • Salvatore Panico
  • Carla H. van Gils
  • N. Charlotte Onland-Moret
  • Aurelio Barricarte
  • Pilar Amiano
  • Kay-Tee Khaw
  • Heiner Boeing
  • Elisabete Weiderpass
  • Eric J. Duell

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: Weused 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; Ptrend 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-muscleinvasive 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.

Original languageEnglish
JournalCancer Epidemiology, Biomarkers & Prevention
Volume29
Issue number8
Pages (from-to)1654-1664
Number of pages11
ISSN1055-9965
DOIs
Publication statusPublished - 2020

    Research areas

  • BLADDER-CANCER RISK, SEX-HORMONES, ASSOCIATION, EXPRESSION, ESTROGEN, THERAPY, SMOKING, IMPACT, WOMEN, DIET

ID: 248848837