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


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.
Hirata
Hiroshi
H
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California-San Francisco, San Francisco, California 94121, USA.
Hinoda
Yuji
Y
Nakajima
Koichi
K
Kikuno
Nobuyuki
N
Suehiro
Yutaka
Y
Tabatabai
Z Laura
ZL
Ishii
Nobuhisa
N
Dahiya
Rajvir
R
D051017:Apoptosis Regulatory Proteins; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015996:Survival Rate
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C090468:TP53BP2 protein, human