Polymorphisms of the endothelial nitric oxide synthase gene in women with vulvar cancer.
OBJECTIVE
Nitric oxide (NO) is involved in angiogenesis and tumor growth. We attempted to establish an association between two polymorphisms of the endothelial nitric oxide synthase (NOS3) gene and vulvar cancer.


METHODS
We used peripheral venous blood sampling, DNA extraction, and polymerase chain reaction (PCR) and pyrosequencing to genotype 68 women with vulvar cancer and 227 healthy Caucasian women for the presence of the intron 4 27-bp-repeat [NOS3*A] and exon 7 Glu298Asp polymorphisms.


RESULTS
The presence of a polymorphic NOS3*A allele (26.2% vs. 24.6%; OR: 1.01; 95% CI: 0.6-2.0; P = 0.9) or a polymorphic NOS3 exon 7 Glu298Asp allele (41.2% vs. 53.7%; OR: 0.6; 95% CI: 0.3-1.0; P = 0.09) was not associated with vulvar cancer. Within the vulvar cancer group, the presence of a polymorphic NOS3*A or a polymorphic NOS3 exon 7 Glu298Asp allele was not associated with clinico-pathological parameters such as advanced tumor stage, groin lymph node involvement, tumor grading, and age at diagnosis. Survival analysis demonstrated that the presence of a polymorphic NOS3*A allele was associated with a significantly reduced disease-free survival time (P = 0.03), whereas the presence of the polymorphic NOS3 exon 7 Glu298Asp allele was not associated with disease-free survival (P = 0.5).


CONCLUSIONS
We are the first to report on NOS3 polymorphisms in vulvar cancer. We found that allelic variation within intron 4, but not ithin exon 7 of NOS3, influences the length of disease-free survival, but not the biological phenotype of vulvar cancer.
Riener
Eva-Katrin
EK
Department of Obstetrics and Gynecology, University of Freiburg, Freiburg, Germany.
Hefler
Lukas A
LA
Grimm
Christoph
C
Galid
Arik
A
Zeillinger
Robert
R
Tong-Cacsire
Dan
D
Gitsch
Gerald
G
Leodolter
Sepp
S
Tempfer
Clemens B
CB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008875:Middle Aged; D009367:Neoplasm Staging; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D014846:Vulvar Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000601:surgery
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III