The bcl2-938CC Genotype Has Poor Prognosis and Lower Survival in Renal Cancer
The bcl2-938CC Genotype Has Poor Prognosis and Lower Survival in Renal Cancer
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DOI：
10.1016/j.juro.2009.03.081
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发表时间：
2009-08-01
影响因子：
6.6
通讯作者：
Dahiya, Rajvir
中科院分区：
文献类型：
--
作者：
Hirata, Hiroshi;Hinoda, Yuji;Dahiya, Rajvir
目的：bcl 2基因存在一个单核苷酸多态性（-938C/A，rs 2279115），其-938A等位基因与Bcl 2表达的相关性显著高于C等位基因。据报道，bcl 2上调与肾癌患者的生存期延长相关。然而，据我们所知，目前还没有关于bcl 2 - 938 C/A单核苷酸多态性在肾细胞癌病例中的作用的信息。因此，我们调查了bcl 2 - 938 C/A位点的多态性及其对肾癌患者临床特征的影响。材料和方法：我们对216例肾癌患者和209例年龄和性别匹配的健康对照进行了bcl 2 - 938 C/A单核苷酸多态性基因分型。采用免疫组化和TUNEL法检测肾癌组织中bcl 2基因-938C/A多态性与Bcl 2表达、增殖和凋亡状态的关系。结果：Bcl 2基因表达阳性的肾癌患者的生存期明显长于Bcl 2基因表达阴性的肾癌患者。在单因素和多因素分析中，bc 12 - 938 CC基因型与不良预后独立相关。Kaplan-Meier分析显示CC基因型患者的生存率显著低于CA+AA基因型患者。CC基因型携带者肾癌组织中Bcl 2表达显著低于CA+AA基因型携带者，而增殖活性显著高于CA+AA基因型携带者。此外，bc 12 - 938 C/A单核苷酸多态性被证明是一个独立的肾细胞癌的不良预后因素。
Purpose: A single nucleotide polymorphism (-938C/A, rs2279115) was found in the bcl2 gene, whose -938A allele is significantly associated with increased Bcl2 expression compared with that of the C allele. Bcl2 up-regulation was reported to be associated with longer survival in patients with renal cancer. However, to our knowledge there is currently no information on the role of the bcl2-938C/A single nucleotide polymorphism in renal cell carcinoma cases. Therefore, we investigated the polymorphism at the bcl2 -938C/A site and its effects on clinical characteristics in patients with renal cell carcinoma.Materials and Methods: We genotyped the bcl2-938C/A single nucleotide polymorphism in 216 patients with renal cancer, and in 209 healthy age and gender matched controls. We also investigated the relationship between the bcl2 -938C/A polymorphism, Bcl2 expression, proliferation and apoptosis status in renal cell carcinoma tissues using immunohistochemistry and TUNEL assay. The association of the bcl2 -938C/A single nucleotide polymorphism with survival in patients with renal cell carcinoma was also analyzed by Kaplan-Meier curves.Results: Survival in Bcl2 positive cases was significantly longer than in negative cases. On univariate and multivariate analyses the bc12 -938CC genotype was independently associated with poor prognosis. Kaplan-Meier analysis showed that survival in patients with CC genotypes was significantly worse than in those with CA+AA genotypes. CC genotype carriers had significantly lower Bcl2 expression and higher proliferative activity in renal cancer tissues than CA+AA genotype carriers.Conclusions: To our knowledge this is the first report to show that the bc12 -938C/C genotype has worse prognosis and lower survival in patients with renal cell carcinoma. In addition, the bc12 -938C/A single nucleotide polymorphism was shown to be an independent adverse prognostic factor for renal cell carcinoma.