Departments of Urology and Clinical Pathology (AH), Medical University of Vienna, Vienna, Austria.
J Urol. 2013 Aug;190(2):717-22. doi: 10.1016/j.juro.2013.01.008. Epub 2013 Jan 9.
Caspase-8 is a key regulator of apoptosis. Its cancer cell antigen induced cell death activity is strongly impacted by the insertion/deletion promoter polymorphism CASP8 -652 6N ins/del (rs3834129). We studied the association of this polymorphism with renal cell carcinoma risk and pathology.
In this hospital based case-control study 500 Austrian patients were genotyped, including 250 with renal cell carcinoma, and 250 age and gender matched healthy controls. Polymerase chain reaction amplified genomic DNA was evaluated by restriction fragment length polymorphism analysis and automatic sequencing. We assessed associations with renal cell carcinoma risk and pathological factors, and performed a meta-analysis of the literature.
The CASP8 -652 6N ins/del polymorphism was significantly linked to renal cell carcinoma (chi-square for trend = 9.50, p = 0.002). Compared with ins/ins, del/del was associated with a 57% decreased risk of the disease (OR 0.43, 95% CI 0.26-0.73, p = 0.002). Furthermore, del/del was associated with a lower risk of distant metastases (p <0.05) but not with T stage, N stage or grade. On meta-analysis the CASP8 -652 6N ins/del polymorphism was associated with renal cell carcinoma risk (p <0.001).
The del/del genotype of the CASP8 -652 6N ins/del promoter polymorphism decreases the overall risk of renal cell carcinoma. It may be associated with a decreased risk of metastasis. Larger studies are warranted to validate our findings.
Caspase-8 是细胞凋亡的关键调节因子。其癌细胞抗原诱导的细胞死亡活性受到插入/缺失启动子多态性 CASP8 -652 6N ins/del（rs3834129）的强烈影响。我们研究了这种多态性与肾细胞癌风险和病理学的关系。
在这项基于医院的病例对照研究中，对 500 名奥地利患者进行了基因分型，包括 250 名肾细胞癌患者和 250 名年龄和性别匹配的健康对照者。通过聚合酶链反应扩增基因组 DNA，并用限制性片段长度多态性分析和自动测序进行评估。我们评估了与肾细胞癌风险和病理因素的关联，并对文献进行了荟萃分析。
Caspase-8 -652 6N ins/del 多态性与肾细胞癌显著相关（趋势 χ2 = 9.50，p = 0.002）。与 ins/ins 相比，del/del 与疾病风险降低 57%相关（OR 0.43，95%CI 0.26-0.73，p = 0.002）。此外，del/del 与远处转移风险降低相关（p <0.05），但与 T 分期、N 分期或分级无关。荟萃分析显示，Caspase-8 -652 6N ins/del 多态性与肾细胞癌风险相关（p <0.001）。
Caspase-8 -652 6N ins/del 启动子多态性的 del/del 基因型降低了肾细胞癌的总体风险。它可能与转移风险降低有关。需要更大的研究来验证我们的发现。
