Introduction & Objectives: In the region of chromosome 19, within the promoter of kallikrein 3 (KLK3) and kallikrein 2 (KLK2) have been identified many loci associated with prostate cancer (PCa) susceptibility. The kallikreine 3 is the PSA gene. Nevertheless, the evidences are still weak. and no major predisposing gene for PCa has still been identified. We present a prospective case control study aimed at identifying the risk of having PCa and the risk of having a high risk cancer based on SNP in the kallikrein 3 promoter and in the region between KLK3 and KLK2 on chromosome 19. Materials & Methods: We extracted DNA from peripheral blood of 1042 patients undergoing prostatic biopsy: 582 consecutive PCa patients (median age 68.8 years - median PSA 6.6 ng/ml) and 460 negative biopsies that served as controls (median age 66.4 years - median PSA 6.5 ng/ml). We examined 8 SNP in KLK3 promoter and 2 SNP in the region between KLK3 and KLK2 by DNA pyrosequencing Results: There was a statistically significant association between SNP rs2735839, rs266882 and cancer susceptibility. Specifically for rs2735839 genotype GA vs. GG and for rs266882 genotype GA vs. AA were associated with an increased risk (OR 1.85, 95% CI 1.36-2.51 and 1.49, 95% CI 1.12-1.99, respectively, p <0.02). The linkage disequilibrium analysis showed a low association (r square 0.04) between the two loci. The figure 1 shows the haplotypes combining the 10 SNP considered and PCa susceptibility. Figure 1 The figure 2 shows the haplotypes combining the 10 SNP considered and high risk cancer (PSA>20 ng/ml or Gleason > 7 or cT3-4) susceptibility. Figure 2 Conclusions: We confirmed the association of SNP rs2735839 with PCa susceptibility. We demonstrated, for the first time, a strong relation between specific haplotypes in the PSA promoter region and the prognosis of PCA, particularly the probability of bearing a high risk PCa.
SINGLE NUCLEOTIDE POLYMORPHISMS (SNP) AND HAPLOTYPES IN PSA PROMOTER: A NEW PROMISING PROSTATE CANCER SUSCEPTIBILITY AND PROGNOSIS PREDICTOR TOOL
GONTERO, Paolo;ZITELLA, Andrea;GIACHINO, Daniela Francesca;DE MARCHI, Mario;TIZZANI, Alessandro
2011-01-01
Abstract
Introduction & Objectives: In the region of chromosome 19, within the promoter of kallikrein 3 (KLK3) and kallikrein 2 (KLK2) have been identified many loci associated with prostate cancer (PCa) susceptibility. The kallikreine 3 is the PSA gene. Nevertheless, the evidences are still weak. and no major predisposing gene for PCa has still been identified. We present a prospective case control study aimed at identifying the risk of having PCa and the risk of having a high risk cancer based on SNP in the kallikrein 3 promoter and in the region between KLK3 and KLK2 on chromosome 19. Materials & Methods: We extracted DNA from peripheral blood of 1042 patients undergoing prostatic biopsy: 582 consecutive PCa patients (median age 68.8 years - median PSA 6.6 ng/ml) and 460 negative biopsies that served as controls (median age 66.4 years - median PSA 6.5 ng/ml). We examined 8 SNP in KLK3 promoter and 2 SNP in the region between KLK3 and KLK2 by DNA pyrosequencing Results: There was a statistically significant association between SNP rs2735839, rs266882 and cancer susceptibility. Specifically for rs2735839 genotype GA vs. GG and for rs266882 genotype GA vs. AA were associated with an increased risk (OR 1.85, 95% CI 1.36-2.51 and 1.49, 95% CI 1.12-1.99, respectively, p <0.02). The linkage disequilibrium analysis showed a low association (r square 0.04) between the two loci. The figure 1 shows the haplotypes combining the 10 SNP considered and PCa susceptibility. Figure 1 The figure 2 shows the haplotypes combining the 10 SNP considered and high risk cancer (PSA>20 ng/ml or Gleason > 7 or cT3-4) susceptibility. Figure 2 Conclusions: We confirmed the association of SNP rs2735839 with PCa susceptibility. We demonstrated, for the first time, a strong relation between specific haplotypes in the PSA promoter region and the prognosis of PCA, particularly the probability of bearing a high risk PCa.
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