Endothelial nitric oxide synthase gene 894G>T, Intron 4a/b, -786C>T polymorphisms in gastric cancer

Muge Tecder-Unal1, Halil G. Karabulut2, Güvem Gumus-Akay2, Yusuf Dolen2, Atila Elhan2, Ajlan Tukun2, A. Ekrem Unal2
1Baskent University, Ankara, Turkey, 2Ankara University, Ankara, Turkey

Nitric oxide, a labile compound synthesized by NOS, is a major regulator not only of physiological vascular tonus but also of the abnormal vascularity associated with tumors. Endothelial production of NO regulates blood flow and angiogenesis, reduces tumor cell adhesion to endothelium. High concentration of NO and its metabolites cause DNA damage during nitration, nitrosation and deamination. Both positive and negative effects on carcinogenesis and tumor growth, apoptosis, cytotoxic mechanisms may be explained by differential susceptibility of tumor cells to NO-mediated reactions. Methods: In this study three major polymorphisms (786T>C, the 27 base pair variable number of tandem repeats in intron 4, and 894G>T) of eNOS gene was investigated in gastric cancer and normal tissues of 50 patients with gastric cancer and in peripheral blood of 98 healthy subjects. Results: We found no significant differences in intron 4a/b and 894G>T (Glu298Asp) allele and genotype frequencies between controls and patient specimens. Nevertheless, the genotype and allele frequencies of 786T>C polymorphism were found to be significantly different between the healthy controls and tumor tissues. Conclusion: The results suggest that eNOS 786T>C polymorphism may play role in the development of gastric cancer.