Vascular invasion in human breast cancer is correlated to T→786C polymorphism of NOS3 gene

• Published in: Nitric oxide 2003-09, Vol.9 (2), p.118-122
• Main Authors: Ghilardi, Giorgio, Biondi, Maria Luisa, Cecchini, Federica, DeMonti, Marco, Guagnellini, Emma, Scorza, Roberto
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Breast cancer; Breast Neoplasms - blood supply; Breast Neoplasms - enzymology; Breast Neoplasms - genetics; Breast Neoplasms - pathology; DNA, Neoplasm - chemistry; DNA, Neoplasm - genetics; Female; Gene promoter polymorphisms; Genetic Predisposition to Disease; Genotype; Humans; Middle Aged; Neovascularization, Pathologic - enzymology; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Nitric oxide synthase; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type III; Pilot Projects; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic - genetics
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2003.09.002

Background. Nitric oxide (NO) is a free radical known to be a major regulator of vascular tonus, to inhibit cell proliferation, induce apoptosis, and be a mediator of macrophage cytostatic and cytotoxic effects. Recently, NO synthesis has been reported to be elevated in different cancers and is expected to promote metastasis by maintaining a vasodilator tone in blood vessels in and around the tumour. Two different common genetic polymorphisms were found on endothelial NO synthase ( NOS3) gene: Glu298Asp on exon 7 and T→786C in the promoter region. Purpose. To evaluate the impact of the NOS3 polymorphisms on vascular invasion and metastasis in breast cancer patients. Design. Two NOS3 gene polymorphisms (Glu298Asp and T→786C) were genotyped in 71 patients operated for breast cancer and followed for 6–30 months (median 21). A control population of 91 age and sex matched tumour-free subjects was also genotyped for the same polymorphisms. Results. The distribution of both polymorphisms was not different between cases and controls. In patients without vascular invasion, T allele frequency was significantly lower than in patients with vascular invasion ( p=0.033). At the end of the follow-up, T allele frequency was found to be less frequent in the metastasis free group than normal population (0.51 vs 0.64; p=0.047). Conclusion. Our results suggest that T allele reduction at the NOS3 promoter region may reduce vascular invasion in breast cancer and consequently reduce metastatic spread and be a favorable prognostic factor. These results need further validation in larger studies.