Bcl2 −938C/A Polymorphism Carries Increased Risk of Biochemical Recurrence After Radical Prostatectomy

Purpose

Approximately 10% to 26% of patients show biochemical failure after radical prostatectomy or radiation therapy. The importance of cell cycle and apoptosis pathways in prostate cancer has been reported. However, to our knowledge there is currently no information on the role of apoptosis and cell cycle related gene polymorphisms in prostate cancer cases. We investigated several polymorphisms related to the cell cycle and apoptosis, and their role in biochemical failure after radical prostatectomy.

Materials and Methods

We genotyped 6 single nucleotide polymorphisms in 6 genes, including p53 (rs1042522), p21 (rs1801270), MDM2 (rs2279744), PTEN (rs701848), GNAS1 (rs7121) and bcl2 (rs2279115), using polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequencing in 140 patients with prostate cancer and 167 age matched controls. The association of polymorphic variants with prostate specific antigen failure in patients with prostate cancer was analyzed by Kaplan-Meier curves.

Results

A significant increase in the frequency of the C/C genotype of GNAS1 rs7121 was observed in patients compared with controls. Interestingly we found a significant difference in biochemical recurrence-free time between the bcl2 C/C and C/A+A/A genotypes. It was also noted that the bcl2 C/C genotype was an independent risk factor for biochemical recurrence after radical prostatectomy on multivariate analysis. There was no statistical difference in the genotype distributions of the other genes between patients and controls.

Conclusions

To our knowledge this is the first report documenting that bcl2 promoter region –938 C/C genotype carriers more frequently show biochemical recurrence than −938C/A+A/A carriers.

Key Words: prostate, prostatic neoplasms, prostate-specific antigen, prostatectomy, polymorphism, genetic

Abbreviations and Acronyms: Bcl, B-cell lymphoma, PC, prostate cancer, PCR, polymerase chain reaction, PSA, prostate specific antigen, PTEN, phosphatase and tensin homologue deleted on chromosome 10, RFLP, restriction fragment length polymorphism, SNP, single nucleotide polymorphism