Polymorphic variants of the CASP3, CASP9, BCL-2 and NKX3-1 genes as candidate markers for prostate cancer susceptibility and poor prognosis.

ABSTRACT

BACKGROUND: There is an ongoing search for molecular markers that are specific, sensitive, and able to predict the stage of prostate cancer (PCa), which is the second most prevalent type of cancer in men worldwide. This study examined whether different single nucleotide polymorphisms (SNPs) were reliable markers of susceptibility to and prognosis of PCa in a sample of Brazilian patients. METHODS AND RESULTS: DNA samples were extracted from peripheral blood cells of 283 PCa patients and matched with samples from healthy controls. Single nucleotide polymorphisms (SNPs in four genes (BCL-2-rs2279115, CASP3-rs4647603, CASP9-rs1052571, and NKX3-1-rs11781886) were genotyped by real-time PCR using the TaqMan® probe. Odds Ratios with 95% confidence intervals were calculated for allelic and genotypic frequencies. The association between polymorphic variants, risk of developing PCa, and clinicopathological characteristics was analyzed by univariate and multivariate logistic regression analysis. SNPs in CASP3, CASP9, and NKX3-1 genes, either alone or in combination (BCL-2+NKX3-1 and CASP3+NKX3-1) were associated with the risk of developing PCa. Genotypes and tumor histopathological data indicated that the BCL-2, NKX3-1, and CASP3 allelic variants, either alone or combined in pairs, were associated with a poor prognosis of PCa. CONCLUSIONS: Genetic polymorphisms in CASP3, NKX3-1, and BCL-2 genes were associated with susceptibility to PCa. The SNPs in the three genes alone and the SNP in the BCL-2 gene combined with the other two genes were strongly associated with adverse outcomes in PCa patients and are promising candidates for molecular markers for PCa prognosis.