Urology Clinic, Istanbul Teaching and Research Hospital, Istanbul, Turkey.
J Urol. 2012 Dec;188(6):2398-403. doi: 10.1016/j.juro.2012.07.096. Epub 2012 Oct 22.
We investigated the relationship between the distribution of the eNOS4a/b polymorphism and the clinical features of superficial bladder cancer.
This study included 201 healthy controls with a mean ± SD age of 62.35 ± 7.96 years and 123 patients with a mean age of 64.03 ± 11.00 years diagnosed with histopathologically confirmed superficial bladder cancer. The eNOS4a/b polymorphism genotype (aa, bb or ab) was identified by polymerase chain reaction. Blood glutathione and plasma malondialdehyde levels were measured by spectrophotometry as an indicator of oxidative stress. We estimated total plasma levels of nitric oxide metabolites using a colorimetric assay kit.
There were no significant differences in age or body mass index between patients and controls. Malondialdehyde and nitric oxide metabolite levels were statistically significantly increased (p = 0.000 and 0.024, respectively) and glutathione levels were decreased (p = 0.000) in patients with superficial bladder cancer. The bb genotype of the eNOS4a/b polymorphism is the most frequent one in the Turkish population and the aa genotype was significantly more common in patients with superficial bladder cancer (p = 0.000). Also, the aa plus ab genotype was significantly more common in patients with high grade tumors (p = 0.013) and in those with more progression to muscle invasive disease (p = 0.000). This genotype was also a significant independent risk factor for recurrence after adjusting for smoking status, stage, grade and the presence of carcinoma in situ on logistic regression analyses (OR 3.095, 95% CI 1.21-7.86, p = 0.018).
The current study suggests that a genotype containing the a allele of the eNOS4a/b polymorphism may be a risk factor for bladder cancer. Additionally, patients harboring the aa plus ab genotype are more likely to experience tumor recurrence and progression.
我们研究了内皮型一氧化氮合酶 4a/b 多态性的分布与浅表膀胱癌临床特征之间的关系。
本研究纳入了 201 名平均年龄（62.35±7.96）岁的健康对照者和 123 名平均年龄（64.03±11.00）岁经组织学证实为浅表膀胱癌的患者。通过聚合酶链反应鉴定内皮型一氧化氮合酶 4a/b 多态性基因型（aa、bb 或 ab）。通过分光光度法测定血液谷胱甘肽和血浆丙二醛水平作为氧化应激的指标。我们使用比色法试剂盒来估计总血浆一氧化氮代谢产物水平。
患者和对照组之间在年龄或体重指数方面无显著差异。患有浅表膀胱癌的患者，丙二醛和一氧化氮代谢物水平显著升高（p=0.000 和 0.024），谷胱甘肽水平降低（p=0.000）。内皮型一氧化氮合酶 4a/b 多态性的 bb 基因型是土耳其人群中最常见的一种，而 aa 基因型在患有浅表膀胱癌的患者中明显更为常见（p=0.000）。此外，aa 加 ab 基因型在高级别肿瘤患者（p=0.013）和更易进展为肌肉浸润性疾病的患者（p=0.000）中更为常见。在调整了吸烟状况、分期、分级和原位癌存在后，这种基因型在 logistic 回归分析中也是复发的显著独立危险因素（OR 3.095，95%CI 1.21-7.86，p=0.018）。
本研究表明，内皮型一氧化氮合酶 4a/b 多态性含有 a 等位基因的基因型可能是膀胱癌的一个危险因素。此外，携带 aa 加 ab 基因型的患者更有可能经历肿瘤复发和进展。
