Estrogen, catechol-O-methyltransferase genotypes, and bladder cancer risk in Egypt

Abstract

Objectives: To examine associations between bladder cancer risk and (1) reproductive history-related estrogen exposure among Egyptian women, and (2) polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men, while taking into account this malignancy's established risk factors. Methods: We used questionnaire and genotype data from an ongoing multicenter case-control study in Egypt. Cases confirmed to have either of the two predominant bladder cancer types, urothelial carcinoma (UC) or squamous cell carcinoma (SCC), and controls, frequency-matched on sex, age, and residence, were included. Results:For Objective (1), we recruited 619 nonsmoking women (429 controls, 190 cases). We found significant associations between increased bladder cancer risk and early menopause (at <45 y old), late first pregnancy (at >18 y old), environmental tobacco smoke (ETS) exposure, and schistosomiasis history. Among postmenopausal women (317 controls, 171 cases), the association between early menopause and increased risk remained significant [adjusted odds ratio (AOR): 1.8; 95% CI: 1.1, 2.8] in the final logistic regression model, which included the variables above, age, residence, and number of pregnancies. For Objective (2), we recruited 952 participants (527 controls, 425 cases). We observed decreased odds of having either bladder cancer type among men with Val/Met or Met/Met genotypes, which encode intermediate- and low-activity enzyme forms, respectively, even after adjusting for covariates, including smoking and schistosomiasis history (AOR: 0.6; 95% CI: 0.4, 0.97); the association was significant for SCC (AOR 0.5; 95% CI: 0. 3, 0.9) and marginally significant for UC (AOR: 0.7; 95% CI: 0.4, 1.1). We detected no significant association between bladder cancer risk and COMT genotypes among postmenopausal women, but the association between reduced SCC risk and Val/Met or Met/Met genotypes approached significance among premenopausal women (n = 43). Conclusions: We found that early menopause was associated with increased odds of having bladder cancer in postmenopausal Egyptian women and that Val/Met or Met/Met COMT genotypes (encoding intermediate- or low-activity enzyme forms) were associated with decreased odds of having SCC in Egyptian men, and possibly also in premenopausal women. These results provide evidence that estrogen exposure and metabolism contribute to bladder cancer development.