Polymorphisms of the Endothelial Nitric Oxide Synthase Gene in Ovarian Cancer

• Published in: Gynecologic oncology Vol. 86; no. 2; pp. 134 - 137
• Main Authors: Hefler, Lukas A., Ludwig, Elisabeth, Lampe, Dieter, Zeillinger, Robert, Leodolter, Sepp, Gitsch, Gerald, Koelbl, Heinz, Tempfer, Clemens B.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.08.2002; Elsevier
• Subjects: Alleles; Analysis of Variance; Austria; Biological and medical sciences; Case-Control Studies; European Continental Ancestry Group - genetics; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Introns; Medical sciences; Nitric Oxide Synthase - genetics; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - surgery; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Tumors; Austria; Human; Enzyme; Malignant tumor; Genetic determinism; Nitric-oxide synthase; Female genital diseases; Polymerase chain reaction; Ovarian diseases; Ovary; Gene; Risk factor; Molecular epidemiology; Female; Genetics; Oxidoreductases; Molecular biology; Polymorphism
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.2002.6749

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.