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  • Title: The CASP8 -652 6N insertion/deletion promoter polymorphism is associated with renal cell carcinoma risk and metastasis.
    Author: de Martino M, Haitel A, Schatzl G, Klingler HC, Klatte T.
    Journal: J Urol; 2013 Aug; 190(2):717-22. PubMed ID: 23313206.
    Abstract:
    PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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