Association of p53 and p21 polymorphisms with prostate cancer

Abstract

Abstract. Cell cycle deregulation is common in human cancer. Alterations of the tumor-suppressor gene p53 and its downstream effector p21 have been indicated in the development of numerous human malignancies. Therefore, we hypothesize that the p53 codon 72 polymorphism, either on its own or in combination with p21 (C98A and C70T) 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 p53 and p21 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 p53 and p21 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 p53 codon 72 arginine (Arg)/proline (Pro)+Pro/Pro and p21 C98A CA genotypes compared to the combined reference genotypes p53 codon 72 Arg/Arg and p21 C98A CC. Neither the p53 genotypes nor the p21 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 p21 C98A CA genotype (OR=0.58; 95% CI, 0.36-0.93; P<0.05) in non-smokers compared to the non-smokers with the p21 C98A CC genotype was observed. Smokers carrying the p53 codon 72 Pro/Pro 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 Arg/Arg genotype. Taken together, to the best of our knowledge this is the first study to show that a combination of the variant genotypes of p53 codon 72 and p21 C98A may modify the prostate cancer risk within the Slovak population.

The effects of p21 gene C98A polymorphism on development of uterine leiomyoma in southeast Iranian women

“…For example Li [38] observed no association between C70T polymorphism and cancer. Recently, in a metaanalysis conducted by Huang on 5963 cases and 8405 controls from 16 published case-control studies, no significant correlation was found between C70T polymorphism and cancer risk neither in dominant model [(T/T + C/T) vs. C/C)] nor in recessive model [T/T vs. (C/C + CT)] [39].…”

Mast cell chymase affects the proliferation and metastasis of lung carcinoma cells in vitro

“…Cell cycle deregulation is common in human cancer. Alterations of the tumor-suppressor protein p53 and its downstream effector, p21, have been indicated in the development of a number of human malignancies (24). The protein p21 is a regulator of cell cycle progression at G 1 and S phase, and, additionally, mediates cellular senescence (37).…”

“…When cellular DNA is damaged, p53 may initiate the synthesis of p21, which is a cyclin-dependent kinase (CDK) inhibitor protein. In turn, p21 may combine with cyclin-CDK to form a trimer which prevents the damaged cells progressing from G 1 to S phase (24).…”

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