Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer.
OBJECTIVE
The free radical nitric oxide is known to be critically involved in ovarian carcinogenesis by inducing apoptosis and by mediating various cytostatic and cytotoxic effects, but also by promoting growth, invasion, and metastasis.


METHODS
We investigated two polymorphisms (exon 7 Glu298Asp and a 27-bp repeat in intron 4) of the gene encoding endothelial nitric oxide synthase (Nos3) in 130 patients with ovarian cancer, 26 patients with borderline ovarian cancer, and 133 healthy age-matched Caucasian women using PCR and pyrosequencing, respectively.


RESULTS
Genotypes and allelic frequencies did not differ between patients with ovarian cancer and controls. Within the ovarian cancer group, however, the presence of at least one mutant allele of intron 4 was associated with advanced tumor stage and positive lymph node involvement, but not with tumor grading. The presence of the mutant allele of exon 7 was not associated with the investigated clinicopathological parameters. No correlation with patients' overall and disease-free survival was ascertained.


CONCLUSIONS
We are the first to report on Nos3 polymorphisms in ovarian cancer. Allelic variation within intron 4 of Nos3 is associated with an advanced tumor stage and positive lymph node involvement in ovarian cancer.
Hefler
Lukas A
LA
Department of Obstetrics and Gynecology, University of Vienna Medical School, Vienna, Austria.
Ludwig
Elisabeth
E
Lampe
Dieter
D
Zeillinger
Robert
R
Leodolter
Sepp
S
Gitsch
Gerald
G
Koelbl
Heinz
H
Tempfer
Clemens B
CB
D000483:Alleles; D000704:Analysis of Variance; D001317:Austria; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007438:Introns; D019001:Nitric Oxide Synthase / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000601:surgery; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D044465:White People / Q000235:genetics*
D019001:Nitric Oxide Synthase