A Functional rs353293 Polymorphism in the Promoter of miR-143/145 Is Associated with a Reduced Risk of Bladder Cancer

Abstract

BACKGROUND AND OBJECTIVES: MicroRNA (miR)-143/145, known as tumor suppressors, can promote cell apoptosis and differentiation, and suppress cell proliferation, invasion and migration. We performed a case-control study to investigate the association of rs353293 in the promoter region of miR-143/145 with bladder cancer risk. METHODS: In total, 869 subjects including 333 cases and 536 controls were enrolled in this study, and the rs353293 polymorphism was genotyped by using a Taqman assay. The promoter activity was measured by the Dual-Luciferase Assay System. RESULTS: We calculated an adjusted odds ratio of 0.64 for the presence of either AA/AG genotypes (95% CI 0.46-0.90) and 0.64 (95% CI 0.47-0.87) for carrying at least one A allele in bladder cancer. Stratified analyses showed that the AA/AG genotypes and the A allele were less prevalent in patients with low grade tumors, compared to those harboring higher grade bladder cancers (adjusted OR = 0.53, 95% CI, 0.30-0.94, P = 0.03 and adjusted OR = 0.54, 95% CI, 0.32-0.92, P = 0.02, respectively). In vitro luciferase reporter analysis showed that rs353293A allele had a lower activity compared with the rs353293G allele (P < 0.001). CONCLUSION: These findings suggest that the functional rs353293 polymorphism may be a useful biomarker to predict the risk of bladder cancer.