Association of and polymorphisms with prostate cancer.

Cell cycle deregulation is common in human cancer. Alterations of the tumor-suppressor gene and its downstream effector p21 have been indicated in the development of numerous human malignancies. Therefore, we hypothesize that the codon 72 polymorphism, either on its own or in combination with ( and ) 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 and 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 and 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 codon 72 arginine ()/proline and CA genotypes compared to the combined reference genotypes p53 codon 72 and CC. Neither the genotypes nor the 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 genotype (OR=0.58; 95% CI, 0.36-0.93; P<0.05) in non-smokers compared to the non-smokers with the CC genotype was observed. Smokers carrying the codon 72 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 genotype. Taken together, to the best of our knowledge this is the first study to show that a combination of the variant genotypes of codon 72 and may modify the prostate cancer risk within the Slovak population.