Genetic risk factors influencing the development of prostate cancer in patients with benign prostatic hyperplasia
The primary aim of this study is to assess the predictive value of six molecular markers in determining PRCa risk in patients with BPH. These molecular markers are: (A)- Two polymorphic repeats, (CAG)n and (GGN)n, in the androgen receptor (AR) gene; (B)- A single nucleotide polymorphism (SNP) in the (-290 A to G) 5' regulatory region of the CYP3A4 gene; (C)- Two SNPs (TaqI and FokI) in vitamin D receptor (VDR) gene; (D)- A SNP (Val655Ile) in the transmembrane domain coding region of HER2 gene. The study evaluated 28 patients who presented with PRCa at least 3 years and up to 15 years after the diagnosis of BPH and 56 matched patients with BPH who did not progress to PRCa over a comparable period. The results of this study showed that CYP3A4 variant genotype identified men with BPH who are at increased risk of developing PRCa (odds ratio 5.2, 95% CI = 1.8-14.3). Similar finding was also seen for VDR TaqI SNP, where TT genotype was associated with a significant 5 fold increase in the risk of developing PRCa in patients previously diagnosed with BPH. Tentative evidence of association between risk of developing PRCa and the variant genotype of HER2 and VDR FokI SNPs was also demonstrated, although the results were not statistically significant. The odds ratio of developing PRCa was 1.88, and 2.33 in BPH patients having HER2 Ile/Ile genotype and VDR FokI FF genotype respectively. This study also showed no evidence for association between the size of AR CAG and GGN repeats and the risk of the development of PRCa in patients with BPH. However, data of this study suggest that BPH patients with AR CAG instability have a 12 fold increase risk in development PRCa. These results provide a potential tool to assist prediction strategies for this important disease.