SPINK1 Promoter Variants Are Associated with Prostate Cancer Predisposing Alterations in Benign Prostatic Hyperplasia Patients.

BACKGROUND/AIM: Several studies reported that patients with benign prostatic hyperplasia (BPH) experienced a 10% increased incidence of prostate cancer (PCa) after the first 5 years of diagnosis. We investigated the association between single nucleotide polymorphisms (SNPs) in the promoter of Serine Protease Inhibitor Kazal Type 1 (SPINK1) and the increased risk of BPH and PCa. MATERIALS AND METHODS: We genotyped three SNPs in a cases-control study, including BPH and PCa cases. Multiple logistic regression models were applied to analyze clinical and genotypic data. RESULTS: We found an inverse association between SNP rs10035432 and BPH under the log-additive (p=0.007) model. No association was found between these SNPs and PCa risk. However, we observed a possible association between rs1432982 and lower-grade PCa (p=0.05) under the recessive model. CONCLUSION: SPINK1 promoter variants are likely to be associated with the risk of BPH.

Analyzing the Association of Polymorphisms in the CRYBB2 Gene with Prostate Cancer Risk in African Americans.

BACKGROUND/AIM: Prostate cancer (PCa) shows disproportionately higher incidence and disease-associated mortality in African Americans. The human crystallin beta B2 (CRYBB2) gene has been reported as one tumor signature gene differentially expressed between African American and European American cancer patients. We investigated the role of CRYBB2 genetic variants in PCa in African Americans. MATERIALS AND METHODS: Subjects comprised of 233 PCa cases and 294 controls. Nine haplotype-tagged single nucleotide polymorphisms (SNPs) in and around the CRYBB2 gene were genotyped by pyrosequencing. Association analyses were performed for PCa with adjustment for age and prostate-specific antigen (PSA), under an additive genetic model. RESULTS: Out of the nine SNPs examined, rs9608380 was found to be nominally associated with PCa (odds ratio (OR)=2.619 (95% confidence interval (CI)=1.156-5.935), p=0.021). rs9306412 was in strong linkage disequilibrium with rs9608380 that showed an association p-value of 0.077. Using ENCODE data, we found rs9608380 mapped to a region annotated with regulatory motifs, such as DNase hypersensitive sites and histone modifications. CONCLUSION: This is the first study to analyze the association between genetic variations in the CRYBB2 gene with PCa. rs9608380, associated with PCa, is a potentially functional variant.

Vitamin D receptor genetic polymorphisms are associated with PSA level, Gleason score and prostate cancer risk in African-American men.

BACKGROUND/AIM: Several studies have revealed an association between single nucleotide polymorphisms (SNPs) in the VDR gene and prostate cancer (PCa) risk in European and Asian populations. To investigate whether VDR SNPs are associated with PCa risk in African-American (AA) men, nine VDR SNPs were analyzed in a case-control study. MATERIALS AND METHODS: Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. RESULTS: rs731236 and rs7975232 were significantly associated with PCa risk (p<0.05). In the analysis of clinical phenotypes, rs731236, rs1544410 and rs3782905 were strongly associated with high PSA level (p<0.05), whereas rs1544410 and rs2239185 showed a statistically significant association with high Gleason score (p<0.05). Haplotype analysis revealed several VDR haplotypes associated with PCa risk. Additionally, a trend existed, where as the number of risk alleles increased in the haplotype, the greater was the association with risk (p-trend=0.01). CONCLUSION: These results suggest that the VDR SNPs may be associated with PCa risk and other clinical phenotypes of PCa in AA men.