Menstrual factors, reproductive history, hormone use, and Urothelial carcinoma risk: A prospective study in the EPIC cohort.
Lujan-Barroso L., Botteri E., Caini S., Ljungberg B., Roswall N., Tjonneland A., Bueno-de-Mesquita B., Gram IT., Tumino R., Kiemeney LA., Liedberg F., Stocks T., Gunter MJ., Murphy N., Cervenka I., Fournier A., Kvaskoff M., Häggström C., Overvad K., Lund E., Waaseth M., Fortner RT., Kühn T., Menéndez V., Sánchez M-J., Santiuste C., Perez-Cornago A., Zamora-Ros R., Cross AJ., Trichopoulou A., Karakatsani A., Peppa E., Palli D., Krogh V., Sciannameo V., Mattiello A., Panico S., van Gils CH., Onland-Moret NC., Barricarte A., Amiano P., Khaw K-T., Boeing H., Weiderpass E., Duell EJ.
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.