Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
J Urol. 2010 Nov;184(5):2150-7. doi: 10.1016/j.juro.2010.06.091. Epub 2010 Sep 17.
We analyzed whether the NOS2 promoter microsatellite (CCTTT)n polymorphism influences bladder cancer pathogenesis.
We genotyped 359 patients with bladder cancer in a population based cohort and 164 population controls by DNA fragment analysis and sequencing. Genotypes were combined with information on tumor stage, grade and stage, grade progression and cancer specific death. Clinical followup was 5 years.
We divided (CCTTT)n alleles into short-10 or fewer, intermediate-11 or 12 and long-13 or greater repeats. Patients homozygous for 13 or longer (CCTTT)n repeats were at decreased odds ratio for bladder cancer (p = 0.010). However, after illness developed they were at 3-fold increased hazard ratio for stage progression (p = 0.062) and 4-fold increased hazard ratio for death from bladder cancer (p = 0.056). We discovered what is to our knowledge a previously undescribed polymorphism at position 23105343 (C/T). There was no difference in frequency between bladder cancer cases and population controls for this polymorphism. No associations were found between tumor stage, grade or stage and grade progression. However, patients with bladder cancer with the heterozygous CT genotype were at 3-fold increased hazard ratio of death from cancer (p = 0.011).
Nitric oxide can induce proliferation or apoptosis depending on the cellular context. Results suggest that the (CCTTT)n NOS2 microsatellite may influence bladder cancer risk and aggressiveness. This polymorphism may have an impact on disease pathogenesis, possibly by affecting intracellular nitric oxide levels.
我们分析了 NOS2 启动子微卫星（CCTTT）n 多态性是否影响膀胱癌的发病机制。
我们通过 DNA 片段分析和测序，对基于人群的队列中的 359 例膀胱癌患者和 164 例人群对照进行了基因分型。将基因型与肿瘤分期、分级、分期和分级进展以及癌症特异性死亡的信息相结合。临床随访时间为 5 年。
我们将（CCTTT）n 等位基因分为短-10 个或更少、中-11 个或 12 个和长-13 个或更长重复。纯合 13 个或更长（CCTTT）n 重复的患者患膀胱癌的比值比降低（p = 0.010）。然而，在疾病发展后，他们的进展期进展风险比增加了 3 倍（p = 0.062），死于膀胱癌的风险比增加了 4 倍（p = 0.056）。我们发现了一个在位置 23105343（C/T）的以前未描述的多态性，据我们所知。该多态性在膀胱癌病例和人群对照之间的频率没有差异。未发现肿瘤分期、分级或分期和分级进展之间存在相关性。然而，膀胱癌患者中杂合性 CT 基因型的患者死于癌症的风险比增加了 3 倍（p = 0.011）。
一氧化氮可以根据细胞环境诱导增殖或凋亡。结果表明，NOS2 微卫星（CCTTT）n 可能影响膀胱癌的风险和侵袭性。这种多态性可能对疾病的发病机制有影响，可能通过影响细胞内一氧化氮水平。
