TY - JOUR

T1 - Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk

T2 - A Prospective Study in the EPIC Cohort

AU - Lujan-Barroso, Leila

AU - Botteri, Edoardo

AU - Caini, Saverio

AU - Ljungberg, Boerje

AU - Roswall, Nina

AU - Tjønneland, Anne

AU - Bueno-de-Mesquita, Bas

AU - Gram, Inger T.

AU - Tumino, Rosario

AU - Kiemeney, Lambertus A.

AU - Liedberg, Fredrik

AU - Stocks, Tanja

AU - Gunter, Marc J.

AU - Murphy, Neil

AU - Cervenka, Iris

AU - Fournier, Agnes

AU - Kvaskoff, Marina

AU - Haeggstroem, Christel

AU - Overvad, Kim

AU - Lund, Eiliv

AU - Waaseth, Marit

AU - Turzanski Fortner, Renee

AU - Kuhn, Tilman

AU - Menendez, Virginia

AU - Sanchez, Maria-Jose

AU - Santiuste, Carmen

AU - Perez-Cornago, Aurora

AU - Zamora-Ros, Raul

AU - Cross, Amanda J.

AU - Trichopoulou, Antonia

AU - Karakatsani, Anna

AU - Peppa, Eleni

AU - Palli, Domenico

AU - Krogh, Vittorio

AU - Sciannameo, Veronica

AU - Mattiello, Amalia

AU - Panico, Salvatore

AU - van Gils, Carla H.

AU - Onland-Moret, N. Charlotte

AU - Barricarte, Aurelio

AU - Amiano, Pilar

AU - Khaw, Kay-Tee

AU - Boeing, Heiner

AU - Weiderpass, Elisabete

AU - Duell, Eric J.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - BLADDER-CANCER RISK

KW - SEX-HORMONES

KW - ASSOCIATION

KW - EXPRESSION

KW - ESTROGEN

KW - THERAPY

KW - SMOKING

KW - IMPACT

KW - WOMEN

KW - DIET

U2 - 10.1158/1055-9965.EPI-20-0184

DO - 10.1158/1055-9965.EPI-20-0184

M3 - Journal article

C2 - 32467345

VL - 29

SP - 1654

EP - 1664

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 8

ER -