Influence of caspases 8 and 9 gene promoter polymorphism on prostate cancer susceptibility and early development of hormone refractory prostate cancer.

Abstract

To investigate, by genotyping CASP8 (-652 6N del/ins) and CASP9 (-1263 A > G; -293 19N del/ins), whether inactivation of apoptosis by genetic polymorphism of caspases 8 and 9 play an integral role in the mechanism of cancer development. To investigate the role of these polymorphisms in susceptibility to early development of hormone refractory prostate cancer. The study included 175 histologically confirmed cases of prostate cancer and 198 age and ethnicity matched healthy controls. CASP9-1263 A > G polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. CASP9-293 del/ins and CASP8-652 del/ins polymorphisms were genotyped and the deletion pattern analysed by polyacrylamide gel electrophoresis. Our results demonstrated that presence of CASP9-1263 G allele was associated with reduced risk for prostate cancer (odds ratio 0.6, 95%CI 0.39-0.92, P= 0.02). Other variant CASP9 was not associated with prostate cancer risk. Coincidentally, the presence of CASP9-1263 G allele was associated with increased risk for progression of prostate cancer to bone metastasis (odds ratio -2.28, 95%CI 1.14-4.53, P= 0.02). CASP8-652 (+/-) genotype was associated with increased hazard for early development of hormone refractory prostate cancer (hazard ratio 2.44, 95%CI 1.2-5.85, P= 0.045). Our results support the hypothesis that variants of CASP9 may influence the susceptibility to prostate cancer and its progression to bone metastasis. CASP8 polymorphism may influence the progression of prostate cancer disease to a hormone refractory state.