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

Leila Lujan-Barroso, Edoardo Botteri, Saverio Caini, Börje Ljungberg, Nina Roswall, Anne Tjønneland, Bas Bueno-de-Mesquita, Inger T. Gram, Rosario Tumino, Lambertus A. Kiemeney, Fredrik Liedberg, Tanja Stocks, Marc J. Gunter, Neil Murphy, Iris Cervenka, Agnès Fournier, Marina Kvaskoff, Christel Häggström, Kim Overvad, Eiliv LundMarit Waaseth, Renée Turzanski Fortner, Tilman Kühn, Virginia Menéndez, Maria Jose Sánchez, 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

Research output: Contribution to journalArticlepeer-review


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; 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-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.

Subject classification (UKÄ)

  • Cancer and Oncology
  • Public Health, Global Health, Social Medicine and Epidemiology

Cite this