Genetic risk factors influencing the development of prostate cancer in patients with benign prostatic hyperplasia

• Main Author: Tayeb, Mohammed Taher
• Published: University of Aberdeen 2002
• Subjects: 616; Prostate
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248613

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 (<i>AR</i>) gene; (B)- A single nucleotide polymorphism (SNP) in the (-290 A to G) 5' regulatory region of the <i>CYP3A4 </i>gene; (C)- Two SNPs (<i>Taq</i>I and <i>Fok</i>I) in vitamin D receptor (<i>VDR</i>) gene; (D)- A SNP (Val655Ile) in the transmembrane domain coding region of <i>HER2</i> 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 <i>CYP3A4</i> 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 <i>VDR Taq</i>I 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 <i>HER2 </i>and <i>VDR Fok</i>I 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 <i>HER</i>2 Ile/Ile genotype and <i>VDR Fok</i>I FF genotype respectively. This study also showed no evidence for association between the size of <i>AR </i>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 <i>AR </i>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.