Estrogen exposure and bladder cancer risk in Egyptian women

To examine associations between reproductive history-related estrogen exposure and urinary bladder cancer in Egyptian women while taking established risk factors into account, we used questionnaire data from an ongoing multicenter case-control study in Egypt [Gender Differences in Bladder Cancer Risk Factors (Loffredo et al., NIH 5R01-CA115618-03, 2006-2011)]. This analysis included controls matched on age and residency site, and cases with confirmed urothelial (transitional) (UC) and squamous cell carcinoma (SCC) of the bladder. We recruited 619 women (429 controls, 190 cases; >98.0% nonsmokers). Unadjusted odds ratios (UORs) indicated that menopause at early age (<45 y), older age at first pregnancy (>18 y), environmental tobacco smoke (ETS) exposure, and schistosomiasis history were significantly associated with increased risk. Among postmenopausal women (317 controls, 171 cases), the association between early menopause and overall bladder cancer risk [(UOR: 2.0; 95% confidence interval (CI): 1.3, 3.0)] remained statistically significant in the logistic regression model [adjusted odds ratio (AOR) 1.8; 95% CI 1.1, 2.8], which included all of the above variables, age, place of residence, and number of pregnancies. Further models by bladder cancer type revealed that early menopause was significantly associated with increased UC risk (AOR: 1.8; 95% CI: 1.1, 3.2), whereas ETS exposure (AOR: 2.2; 95% CI: 1.2, 4.1) and schistosomiasis history (AOR 1.1; 95% CI 1.0, 1.2) were significantly associated with increased SCC risk. Given increasing bladder cancer incidence and recurrence worldwide, these findings suggest that public health efforts to reduce modifiable risk exposures should consider including estrogen therapy and ETS mitigation options.