Bladder Cancer and NOS-NO Gene Polymorphısms

Akın S Amasyalı ,Bülent Erol,Ercan Kazan

doi:10.17554/j.issn.2410-0579.2015.01.7

Abstract

Nitric oxide (NO) is a pleiotropic molecule with a variety of functions. NO may have both pro- and antitumor functions. NO could take part in tumour development and progression. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may infuence the risk of cancer, but the results are still conflicting. Most studied eNOS gene mutations are T-786C, G894T and intron 4a/b polymorphisms in the literature. Environmental factors and genetic susceptibility may contribute to cancer development. Numerous clinical and molecular studies have shown that bladder cancer is a heterogeneous disease. Different chemical carcinogens are associated with similar levels of risk for developing varying grades and stages of bladder cancer, and therefore, carcinogen exposure alone cannot explain the heterogeneity of the disease. Molecular alterations may lead to heterogeneity and are influenced by environmental exposure. There are many genetic polymorphisms in metabolic enzymes, and other genes have been found to be bladder cancer risk factors. But a few studies have evaluated the role of eNOS polymorphisms in a this cancer. The objective of this review is to evaluate the role of the eNOS polymorphisms in cancer susceptibility, especially in bladder cancer which is the second most common malignancy of urinary tract.

Highlights

Bladder cancer is one of the most common cancers in the world. This cancer is the second most common malignancy of urinary tract cancer and fourth most frequent cancer diagnosed in men accounting for 7% of total cancers and the eighth most common cancer in women in the United States[1]
Importance of Nitric oxide synthase (NOS) gene polymorphisms relies on the contradictory role of Nitric oxide (NO) in carcinogenesis
Several polymorphisms identified in human endothelial nitric oxide synthase (eNOS) gene but a few variations are assumed to have functional importance[5,6]

Summary

Introduction

Bladder cancer is one of the most common cancers in the world. This cancer is the second most common malignancy of urinary tract cancer and fourth most frequent cancer diagnosed in men accounting for 7% of total cancers and the eighth most common cancer in women in the United States[1]. Three main isoforms, derived from separate genes, have been described and named after the cells in which they were first found[3]. These are neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2) and endothelial NOS (eNOS or NOS3)[4]. NOS isoforms are reported to be present in human solid tumors and tumor cell lines (Table 1). Importance of NOS gene polymorphisms relies on the contradictory role of NO in carcinogenesis. Several polymorphisms identified in human eNOS gene but a few variations are assumed to have functional importance[5,6]. Several studies reported that some of the eNOS gene polymorphisms are significantly associated with development of several types of cancer[7,8]

Objectives

Findings

Conclusion