Polymorphisms in nitric-oxide synthase 3 may influence the risk of urinary-bladder cancer

► We analyzed if two NOS3 polymorphism influence risk and pathogenesis of bladder cancer. ► Allelic discrimination and sequencing were used to genotype patients and controls. ► Patient genotypes were combined with information from a 5-year clinical follow-up. ► The NOS3 promoter polymorphism −786T>C (rs2070744) may influence bladder cancer risk. 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.