Endothelial nitric oxide synthase gene polymorphism in gastric cancer.

Background/aims: Nitric oxide, a labile compound synthesized by nitric oxide synthase, is a major regulator not only of physiological vascular tonus but also of the abnormal vascularity associated with tumors. Endothelial production of nitric oxide regulates blood flow and angiogenesis and reduces tumor cell adhesion to the endothelium. A high concentration of nitric oxide and its metabolites causes DNA damage during nitration, nitrosation and deamination. Both positive and negative effects on carcinogenesis and tumor growth, apoptosis, and cytotoxic mechanisms may be explained by differential susceptibility of tumor cells to nitric oxide-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 the endothelial nitric oxide synthase gene were investigated in gastric cancer and normal tissues of 50 patients with gastric cancer and in the 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 control 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.
Conclusions: The results suggest that endothelial nitric oxide synthase 786T>C polymorphism may play a role in the development of gastric cancer.