Association of p53 and p21 polymorphisms with prostate cancer

Abstract

Cell cycle deregulation is common in human cancer. Alterations of the tumor-suppressor gene <i>p53</i> and its downstream effector p21 have been indicated in the development of numerous human malignancies. Therefore, we hypothesize that the <i>p53</i> codon 72 polymorphism, either on its own or in combination with <i>p21</i> (<i>C98A</i> and <i>C70T</i>) polymorphisms, modifies the risk of prostate cancer within the Slovak population, and no previous studies have investigated these gene-gene interactions in the pathogenesis of prostate cancer in the Slovak population. Polymerase chain reaction-restriction fragment length polymorphism was used to determine the <i>p53</i> and <i>p21</i> genotypes in subjects comprising 300 prostate cancer patients and 446 healthy individuals. These 3 polymorphisms individually did not correlate with the prostate cancer risk. Conversely, the interaction between the <i>p53</i> and <i>p21</i> polymorphisms significantly decreased the risk of prostate cancer, with the odds ratio (OR) being 0.49 [95% confidence interval (CI), 0.27-0.86; P<0.05] for subjects carrying the <i>p53</i> codon 72 arginine (<i>Arg</i>)/proline <i>(Pro)+Pro/Pro</i> and <i>p21 C98A</i> CA genotypes compared to the combined reference genotypes p53 codon 72 <i>Arg/Arg</i> and <i>p21 C98A</i> CC. Neither the <i>p53</i> genotypes nor the <i>p21</i> genotypes showed statistically significant differences in Gleason score or serum prostate-specific antigen levels (P>0.05). A decreased risk of prostate cancer association with the <i>p21 C98A CA</i> genotype (OR=0.58; 95% CI, 0.36-0.93; P<0.05) in non-smokers compared to the non-smokers with the <i>p21 C98A</i> CC genotype was observed. Smokers carrying the <i>p53</i> codon 72 <i>Pro/Pro</i> genotype were not at any significant risk of prostate cancer (OR=2.97; 95% CI, 0.51-17.15) compared to the non-smokers with the <i>Arg/Arg</i> genotype. Taken together, to the best of our knowledge this is the first study to show that a combination of the variant genotypes of <i>p53</i> codon 72 and <i>p21 C98A</i> may modify the prostate cancer risk within the Slovak population.