The bcl2 −938CC Genotype Has Poor Prognosis and Lower Survival in Renal Cancer
Received 31 October 2008 published online 18 June 2009.
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.
aDepartment of Urology, San Francisco Veterans Affairs Medical Center and University of California-San Francisco, San Francisco, California
bDepartment of Pathology, San Francisco Veterans Affairs Medical Center and University of California-San Francisco, San Francisco, California
cDepartment of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
dDepartment of Urology, Toho University Faculty of Medicine, Tokyo, Japan
Correspondence: Urology Research Center (112F), Veterans Affairs Medical Center and University of California-San Francisco, 4150 Clement St., San Francisco, California 94121 (telephone: 415-750-6964; FAX: 415-750-6639)
Study received Shimane Medical University and Toho University approval.
Supported by National Institutes of Health Grants RO1CA101844, R01CA111470 and T32-DK07790, a Veterans Affairs REAP award, Merit Review grants and the Yamada Science Foundation.
ABSTRACT