Impact of endothelial nitric oxide synthase polymorphisms on urothelial cell carcinoma development

Objectives: Urothelial cell carcinoma (UCC), a major malignancy of the genitourinary tract, is induced through carcinogenic etiological factors. Endothelial nitric oxide synthase (eNOS) is one of the major isoforms of nitric oxide synthase and is involved in various pathophysiologic and physiologic processes. In this study, eNOS single-nucleotide polymorphisms were investigated to evaluate UCC susceptibility and clinicopathological characteristics. Materials and methods: Two single-nucleotide polymorphisms of eNOS in 431 patients with UCC and 862 controls without cancer were analyzed using real-time polymerase chain reaction. Results: The results showed that 272 men with UCC having eNOS 894 G > T rs1799983 “GT + TT” variants had a high risk of developing a large tumor (T1–T4, P = 0.038). Furthermore, a correlation was observed between the expressions of eNOS and invasive tumor, metastasis and poor survival in urothelial carcinoma in The Cancer Genome Atlas data set. Conclusion: Our results indicated that male patients with UCC carrying eNOS 894 G > T rs1799983 “GT + TT” genetic variants have a high risk of developing a large tumor, and eNOS polymorphisms may serve as a marker or therapeutic target in UCC treatment.