Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden.
Nitric Oxide. 2011 Oct 30;25(3):338-43. doi: 10.1016/j.niox.2011.06.003. Epub 2011 Jun 13.
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.
一氧化氮（NO）是一种重要的生物信使，已知其能影响多种人类癌症。NO 的形成是由三种不同的一氧化氮合酶（NOS）催化的。在这项研究中，我们分析了 NOS3 启动子多态性-786T>C（rs2070744）和 NOS3 谷氨酸 298 天冬氨酸多态性（rs1799983）是否影响膀胱癌的风险和发病机制。等位基因鉴别和 DNA 测序用于确定 359 例基于人群的膀胱癌患者和 164 例人群对照中的-786T>C 和 Glu298Asp NOS3 基因型。使用 5 年临床随访，将患者基因型与肿瘤分期、分级、分期和分级进展以及癌症特异性死亡的信息相结合。-786T>C 启动子多态性的 C 等位基因纯合携带者患膀胱癌的几率增加了三倍（p=0.017）。未发现 Glu298Asp 多态性与膀胱癌风险增加相关，但 Glu298Asp 与肿瘤分级之间存在关联（p=0.040）。我们的结果表明，NOS3 启动子多态性-786T>C 可能影响膀胱癌的风险。
