Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer

Abstract

Tumor protein 53 (<i>TP53</i>), a tumor suppressor gene, is a vital cellular cancer suppressor in multicellular organisms. Murine double minute-2 (MDM2) is an oncoprotein that inhibits TP53 activity. A number of studies have examined the association of <i>TP53</i> and <i>MDM2</i> polymorphisms with the risk of common forms of cancer, but the findings remain inconclusive. The present study aimed to evaluate the impact of the 40-bp insertion/deletion (I/D) polymorphism (rs3730485) in the <i>MDM2</i> promoter region and the 16-bp I/D polymorphism (rs17878362) in <i>TP53</i> on the susceptibility of prostate cancer (PCa) in a sample of the Iranian population. This case-control study included 103 patients with pathologically confirmed PCa and 142 patients with benign prostatic hyperplasia. The <i>MDM2</i> 40-bp I/D and <i>TP53</i> 16-bp I/D polymorphism was determined using polymerase chain reaction analysis. The results demonstrated that the <i>MDM2</i> 40-bp I/D polymorphism increased the risk of PCa in a co-dominant inheritance model [odds ratio (OR)=1.88; 95% confidence interval (CI)=1.11-3.19; P=0.023, D/D vs. I/I], while this variant marginally increased the risk of PCa in a dominant model (OR=1.69; 95% CI=1.00-2.83; P=0.051, I/D+D/D vs. I/I). No significant association was observed between the <i>TP53</i> 16-bp I/D polymorphism and PCa. In conclusion, the present study demonstrated that the 40-bp I/D polymorphism in the <i>MDM2</i> promoter increased the risk of PCa in an Iranian population. Further investigations with diverse ethnicities and larger sample sizes are required to verify these results.