SNPs may have a functional role in causing amino acid changes, mRNA transcript instability and transcription factor binding affinity variations (21–23). In this study, we characterized 13 different SNPs utilizing TaqMan Real Time PCR assays. The rs16901979 SNP showed significant differences in allele and genotype frequencies. The rs16901979A allele was found at a higher frequency in PC patients than in normal healthy controls, and individuals with this allele were 3.3 times more susceptible to PC. However, no significant difference was observed between the nodular hyperplasia patients and normal healthy controls. Accordingly, this SNP may be considered a risk genetic factor for PC disease but not for nodular hyperplasia development. A comparison of the genotype model for rs16901979 (C/C vs A/C) has shown that individuals with the A/C genotype are at 5 times higher risk for PC development than those with the C/C genotype but not for nodular hyperplasia. Additionally, we observed a minor presence of the A/A genotype among the three groups. The presence of this genetic component may indicate its lethal effect for carrier individuals among the Saudi population. The rs16901979 SNP was found to be associated with PC cancer in a case control study by Robbins et al. that included 490 prostate cancer patients and 567 healthy controls of African American individuals (24). A similar association was found in a Taiwanese study by Chen et al. (25). In a multicenter study of the Swedish population that included 2893 patients with PC and 1781 control subjects, rs16901979 was also found to be associated with PC (12). The Rs16901979 SNP is present within the non-protein-coding region of the CASC8 gene, located at 8q24 of the human genome map. GWAS and several case–control studies have demonstrated the association of specific variants in the CASC8 gene with prostate cancer(26), and it has been suggested that 8q24 regions can independently influence the risk for prostate cancer development and advanced disease status in particular (27).
Additionally, the rs629242T allele was found at a significantly higher frequency among PC patients than among healthy normal controls. In general, rs629242T is observed less frequently than rs629242C, which is classified as the mutated allele for the rs629242 SNP (23) and is considered a risk factor for PC occurrence with a 1.6 odds ratio. A study investigating the role of rs629242 in PC found that the rs629242T allele infers a 29% increased risk for disease progression in the African American population (28). The rs629242 SNP is present within the KIAA1211 gene located at the 4q12 region. This gene encodes an actin cytoskeletal regulator that plays a role in maintaining the integrity of epithelial cells and suppressing tumorigenesis (29).
The rs1447295A allele was found at a significantly lower rate in benign nodular hyperplasia patients than in normal healthy controls or PC groups but with no difference between the healthy controls and PC. This result is in keeping with findings obtained by Robbins et al., who concluded that there is no association between the rs1447295 SNP and PC and among the African American population (24,30). However, the rs1447295 SNP was demonstrated to be associated with PC and related clinical covariables in northern Chinese men(31) and in a meta-analysis study performed by Cheg et al.(27). These contradictions may be observed because the interaction between genetic susceptibility and environmental factors plays an important role in disease development (24,30). Based on our findings, we suggest that this rs1447295 SNP may be used as a genetic marker to differentiate between benign and malignant tumors in Saudi males with prostatic disease.