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


OBJECTIVE
To evaluate the impact of the NOS3 polymorphisms on vascular invasion and metastasis in breast cancer patients.


METHODS
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).


CONCLUSIONS
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.
Ghilardi
Giorgio
G
Dipartimento MCO, Clinica Chirurgica Generale, Università degli Studi di Milano, Polo S Paolo, Via A Di Rudini;, 8, I-20142 Milan, Italy. giorgio.ghilardi@unimi.it
Biondi
Maria Luisa
ML
Cecchini
Federica
F
DeMonti
Marco
M
Guagnellini
Emma
E
Scorza
Roberto
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
D004273:DNA, Neoplasm; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III