title: Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Vienna Medical School, Vienna, Austria.
authors.forename: Lukas A
authors.initials: LA
authors.lastname: Hefler
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ludwig
authors.forename: Dieter
authors.initials: D
authors.lastname: Lampe
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.forename: Sepp
authors.initials: S
authors.lastname: Leodolter
authors.forename: Gerald
authors.initials: G
authors.lastname: Gitsch
authors.forename: Heinz
authors.initials: H
authors.lastname: Koelbl
authors.forename: Clemens B
authors.initials: CB
authors.lastname: Tempfer
mesh_terms: 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*
chemical_list: D019001:Nitric Oxide Synthase