title: Association ofp53andp21polymorphisms with prostate cancer.
abstract: Cell cycle deregulation is common in human cancer. Alterations of the tumor-suppressor genep53and its downstream effector p21 have been indicated in the development of numerous human malignancies. Therefore, we hypothesize that thep53codon 72 polymorphism, either on its own or in combination withp21(C98AandC70T) 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 thep53andp21genotypes 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 thep53andp21polymorphisms 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 thep53codon 72 arginine (Arg)/proline(Pro)+Pro/Proandp21 C98ACA genotypes compared to the combined reference genotypes p53 codon 72Arg/Argandp21 C98ACC. Neither thep53genotypes nor thep21genotypes showed statistically significant differences in Gleason score or serum prostate-specific antigen levels (P>0.05). A decreased risk of prostate cancer association with thep21 C98A CAgenotype (OR=0.58; 95% CI, 0.36-0.93; P<0.05) in non-smokers compared to the non-smokers with thep21 C98ACC genotype was observed. Smokers carrying thep53codon 72Pro/Progenotype were not at any significant risk of prostate cancer (OR=2.97; 95% CI, 0.51-17.15) compared to the non-smokers with theArg/Arggenotype. Taken together, to the best of our knowledge this is the first study to show that a combination of the variant genotypes ofp53codon 72 andp21 C98Amay modify the prostate cancer risk within the Slovak population.
authors.affiliation: Department of Medical Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine, 036 01 Martin, Slovak Republic.
authors.forename: Monika Kmeťová
authors.initials: MK
authors.lastname: Sivoňová
authors.affiliation: Department of Medical Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine, 036 01 Martin, Slovak Republic.
authors.forename: Marta
authors.initials: M
authors.lastname: Vilčková
authors.affiliation: Department of Urology, Comenius University in Bratislava, Jessenius Faculty of Medicine and UHM, 036 01 Martin, Slovak Republic.
authors.forename: Ján
authors.initials: J
authors.lastname: Kliment
authors.affiliation: Department of Medical Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine, 036 01 Martin, Slovak Republic.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mahmood
authors.affiliation: Department of Medical Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine, 036 01 Martin, Slovak Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Jurečeková
authors.affiliation: Department of Urology, Comenius University in Bratislava, Jessenius Faculty of Medicine and UHM, 036 01 Martin, Slovak Republic.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dušenková
authors.affiliation: Department of Nuclear Physics and Biophysics, Division of Biomedical Physics, Comenius University, Faculty of Mathematics, Physics and Informatics, 842 48 Bratislava, Slovak Republic.
authors.forename: Iveta
authors.initials: I
authors.lastname: Waczulíková
authors.affiliation: Institute of Simulation and Virtual Medical Education, Comenius University, Faculty of Medicine, 813 72 Bratislava, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Slezák
authors.affiliation: Department of Medical Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine, 036 01 Martin, Slovak Republic.
authors.forename: Dušan
authors.initials: D
authors.lastname: Dobrota
keywords: Slovak population; cigarette smoking; p21; p53; prostate cancer