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Updated: May 31, 2026

Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors
Published on: March 29, 2019
Polymorphisms in nitric-oxide synthase 3 may influence the risk of urinary-bladder cancer
Charlotta Ryk1, N Peter Wiklund, Tommy Nyberg
1Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden.
Abstract:
Nitric oxide (NO) is an important biological messenger known to influence several types of human cancers. NO formation is catalyzed by three different nitric oxide synthase (NOS) enzymes. In this study we analyzed if the NOS3 promoter polymorphism -786T>C (rs2070744) and the NOS3 Glu298Asp polymorphism in exon 7 (rs1799983) influence risk and pathogenesis of urinary-bladder cancer. Allelic discrimination and DNA sequencing were used to determine the -786T>C and the Glu298Asp NOS3 genotypes in 359 urinary-bladder cancer patients, from a population-based patient material, and 164 population controls. Patient genotypes were combined with information on tumor stage, grade, stage and grade progression and cancer-specific death, using a 5-year clinical follow-up. A threefold increased odds ratio for bladder cancer was found in homozygous carriers of the C allele of the -786T>C promoter polymorphism (p=0.017). No increased bladder cancer risk was found for the Glu298Asp polymorphism, but there was an association between the Glu298Asp and tumor grade (p=0.040). Our results suggest that the NOS3 promoter polymorphism -786T>C may influence bladder cancer risk.
Insights
The NOS3 gene
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Nitric oxide (NO) plays a role in human cancers.
- Nitric oxide synthase (NOS) enzymes catalyze NO formation.
- The NOS3 gene encodes endothelial NOS.
Purpose of the Study:
- To investigate the association between NOS3 gene polymorphisms and urinary-bladder cancer risk and pathogenesis.
- To analyze the NOS3 promoter -786T>C (rs2070744) and Glu298Asp (rs1799983) polymorphisms.
Main Methods:
- Genotyping using allelic discrimination and DNA sequencing.
- Analysis of 359 bladder cancer patients and 164 controls.
- Correlation of genotypes with tumor stage, grade, progression, and survival.
Main Results:
- A threefold increased odds ratio for bladder cancer in homozygous carriers of the NOS3 -786T>C promoter polymorphism C allele (p=0.017).
- No significant association between the NOS3 Glu298Asp polymorphism and bladder cancer risk.
- An association found between the NOS3 Glu298Asp polymorphism and tumor grade (p=0.040).
Conclusions:
- The NOS3 promoter polymorphism -786T>C may be a risk factor for bladder cancer.
- The NOS3 Glu298Asp polymorphism might be associated with bladder cancer progression.
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