Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt

Abstract

Objectives To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men. Materials and methods We used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively. Results The study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n=169), and 527 controls. The odds of having either type of bladder cancer was lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0. 34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women. Conclusions These findings suggest that, even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared to women in South Egypt.

Significant Association of Catechol-O-Methyltransferase Val158Met Polymorphism with Bladder Cancer Instead of Prostate and Kidney Cancer

“…In addition, it has been said that estrogens could protect against bladder cancer (42,43). Meanwhile, among postmenopausal women who did not have high levels of estradiol with a lowactivity COMT genotype, the significant association of COMT and bladder cancer was absent (28). Based on these findings, we believe that the COMT Val158Met polymorphism could increase the level of estradiol and protect against bladder cancer to some extent.…”

“…Wolpert et al (28) in 2012 studied the relation of the COMT Val158Met polymorphism to bladder cancer in different sexes; the results suggested that the association was statistically significant for squamous cell carcinoma of the bladder. (38)(39)(40).…”

Agricultural Workers and Urinary Bladder Cancer Risk in Egypt

“…In Egypt, urinary bladder cancer incidence is among the highest worldwide, 9,29 and SCC currently represents approximately 30% of all current cases; 30-31 this is a significant shift from 60-70% of bladder cancer cases reported before the 1980’s and Schistosoma hematobium eradication campaigns. 9 Furthermore, a large portion of Egypt’s population is employed in farming.…”

Pesticides, Gene Polymorphisms, and Bladder Cancer Among Egyptian Agricultural Workers

“…48,49 Indeed, such a mechanism was demonstrated for the enzymes encoded by gene variants of the glutathione S-transferase, 50,51 and for catechol-O-methyltransferase. 52 Our finding that agricultural workers with combined low activity NQO1 and high activity SOD2 genotypes had slightly higher risk than those with either one alone can possibly be due to an accumulation of ROS as results of its increased production by an active SOD2 and decreased removal by a less active NQO1 .…”