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

Ming-Dow Tsay; Ming-Ju Hsieh; Shian-Shiang Wang; Wen-Chen Wang; Ya-Yi Chou; Chen-Ho Shih; Shun-Fa Yang; Ying-Erh Chou

doi:10.1016/j.urolonc.2018.12.023

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

Urol Oncol. 2019 Apr;37(4):293.e1-293.e9. doi: 10.1016/j.urolonc.2018.12.023. Epub 2019 Jan 2.

Authors

Ming-Dow Tsay¹, Ming-Ju Hsieh², Shian-Shiang Wang³, Wen-Chen Wang⁴, Ya-Yi Chou⁴, Chen-Ho Shih⁴, Shun-Fa Yang⁵, Ying-Erh Chou⁶

Affiliations

¹ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Family medicine, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
² Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
³ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
⁴ School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
⁵ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁶ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: ysf@csmu.edu.tw.

PMID: 30611644
DOI: 10.1016/j.urolonc.2018.12.023

Abstract

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.

Keywords: Polymorphism; Transitional cell carcinoma; eNOS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Carcinoma, Transitional Cell / genetics*
Carcinoma, Transitional Cell / pathology
Female
Humans
Male
Nitric Oxide Synthase Type III / genetics*
Polymorphism, Single Nucleotide / genetics*
Urinary Bladder Neoplasms / genetics*
Urinary Bladder Neoplasms / pathology

Substances

Nitric Oxide Synthase Type III