*Corresponding author email: ilhanyaylim@gmail.com Symbiosis Group Symbiosis Group Symbiosis www.symbiosisonline.org www.symbiosisonlinepublishing.com ISSN Online: 2377-4274 Investigation Of Nitric Oxide Synthase 3 (Nos3) Glu298asp Gene Variation In Breast Cancer Patients Canan Cacina 1,2 ,6 , Cem Horozoglu 1,2 6 , Oncu Koc Erbasoglu 1 , Bahar Toptas 1 , Yemliha Yildiz 1 , Soykan Arıkan 3 , Seden Kucucuk 4 , İlhan Yaylım 1 and Turgay İsbir 5 1 Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, İstanbul-Turkey 2 Department of Medical Services and Techniques, Istanbul Gelisim University, Istanbul-Turkey 3 Clinic of Surgery, Istanbul Training and Research Hospital, Istanbul-Turkey 4 Department of Radiation Oncology, Institute of Oncology, Istanbul University, İstanbul-Turkey 5 Department of Medical Biology, Faculity of Medicine, Yeditepe University, İstanbul 6 Both authors contributed equally to this work. International Journal of Genetic Science Open Access Research Article Abstract The role of Nitric Oxide (NO) in tumor biology is not well understood. However, it has been proposed that NO is a highly reactive free radical and plays important roles in growth, progression or metastasis of tumour. Nitric oxide syntheses (NOSs) are a family of enzymes that catalyzing the production of NO by converting L-arginine to L-citrulline. The aim of present study was to examine Nitric Oxide Synthase 3 (NOS3) Glu298Asp polymorphism in patients with breast cancer. For this purpose, 49 patients with breast cancer and 89 healthy controls were included in the study. The NOS3 Glu298Asp polymorphism was genotyped by PCR-RFLP using peripheral blood samples in our study groups. NOS3 Glu298Asp genotype distribution in the breast cancer patients was statistically different from the healthy control group NOS3 Glu298Asp gene variation T allele frequency was significantly higher in breast cancer patients that of controls. Our finding suggests that NOS3 Glu298Asp might be associated with breast cancer risk. Key words : Oxidative stress; NOS3; breast cancer. Received: March 28, 2018; Accepted: September 11, 2018; Published: September 20, 2018 *Corresponding author: İlhan Yaylim, Istanbul University, Aziz Sancar Institute for Experimental Medicine, Department of Molecular Medicine, Vakif Gureba Cad. Capa 34390 Istanbul Turkey, Tel: +90 0212 6351959, Fax: +90 0212 6351959, e-mail address: ilhanyaylim@gmail.com Introduction Breast cancer is one of the most common types of cancer in the world and is ranked first among the most commonly diagnosed cancers in women and second among the most commonly cause of death in cancer [1].Known risk factors for breast cancer include family history, age, first gestational age, alcohol consumption, postmenopausal obesity, and ionizing radiation. However, all these factors are insufficient to understand the etiology of breast cancer and its geographical variation [2].The heterogeneity of genes involved in oxidative stress and metabolism of carcinogens can also affect the susceptibility to breast cancer [3]. Free radical nitric oxide (NO) is an important biological mediator that plays a role in various cytostatic and cytotoxic functions and is associated with apoptosis, metastasis and angiogenesis [4].Reactive nitrogen species, derived from NO and NO, by leading to oxidative and nitrosative stress,cause DNA damage and DNA repair enzymes to be inhibited by direct or indirect mechanisms [5].Nitric oxide (NO) is synthesized by Nitric Oxide Synthase (NOS) is forms during L-sitrulinin, L-arginine conversion [6, 7].NO has tumor growth and tumor angiogenesis stimulation and metastasis-activating effects at low concentrations, whereas at higher concentrations, tumor cells play a role in apoptosis processing and tumor growth arrest [8]. Changes in the balance between cell proliferation and apoptosis contribute to the pathogenesis of many diseases. NO can change this balance because it is toxic or protective depending on the concentration, cell type and environmental conditions, it can cause or inhibit apoptosis [9].In endothelial cells, there are two forms of Nitric Oxide Sentetase (NOS), the inducible NOS encoded by the NOS2 gene and the endothelial NOS encoded by the NOS3 gene [10].NOS3 is encoded by a 26 exon gene on chromosome 7 [11].The Glu298Asp variant of NOS3is one of the common polymorphisms seen in this gene and is characterized by glutamate-aspartate exchange (G-T) for codon 298 at nucleotide 894. In some studies it has been concluded that NOS3 Glu298Asp (894G> T) mutant TT variant may be associated with breast cancer [12]. In our study, it was aimed to determine genotype and allele frequencies in patient and control subjects in order to investigate the importance of NOS3 gene Glu298Asp polymorphism in breast cancer susceptibility. At the same time, the relationship between the clinical and prognostic parameters of the disease and NOS3 polymorphism was examined in patients with breast cancer. Materials And Methods In our study, 49 breast cancer patients were included in the patient group and 89 healthy individuals were included in