The bcl2 −938CC Genotype Has Poor Prognosis and Lower Survival in Renal Cancer

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 bcl2 −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 bcl2 −938C/C genotype has worse prognosis and lower survival in patients with renal cell carcinoma. In addition, the bcl2 −938C/A single nucleotide polymorphism was shown to be an independent adverse prognostic factor for renal cell carcinoma.

Key Words: kidney, carcinoma, renal cell, polymorphism, single nucleotide, apoptosis, genotype

Abbreviations and Acronyms: Bcl2, B-cell lymphoma, IHC, immunohistochemistry, PCR, polymerase chain reaction, PI, proliferation index, RCC, renal cell carcinoma, RFLP, restriction fragment length polymorphism, SNP, single nucleotide polymorphism