The bcl2 -938CC genotype has poor prognosis and lower survival in renal cancer

• Published in: The Journal of urology Vol. 182; no. 2; p. 721
• Main Authors: Hirata, Hiroshi, Hinoda, Yuji, Nakajima, Koichi, Kikuno, Nobuyuki, Suehiro, Yutaka, Tabatabai, Z Laura, Ishii, Nobuhisa, Dahiya, Rajvir
• Format: Journal Article
• Language: English
• Published: United States 01.08.2009
• Subjects: Apoptosis Regulatory Proteins; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Carrier Proteins - genetics; Female; Genotype; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - mortality; Male; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Survival Rate
• ISSN: 1527-3792
• DOI: 10.1016/j.juro.2009.03.081

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. 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. 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. 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.