Association of p53 polymorphisms with breast cancer: a case-control study in Slovak population

Abstract

Protein p53 is the tumor suppressor involved in cell cycle control and apoptosis. As a transcription factor p53 controls many cell processes and helps in prevention of cancer development. The p53 gene is polymorphic. Polymorphisms can affect the important regions involved in protein tumor suppressor activity. The well-known polymorphisms are the polymorphisms BstUI in exon 4 and MspI in intron 6. Both are supposed to be associated with cancer development. The purpose of this study was to investigate the genotype frequencies and associations of these polymorphisms with breast cancer in Slovak population. We observed the prevalence of BstUIPro (27.47%) and MspIA1 (17.58%) alleles and BstUIPro/Pro (8.79%) and MspIA1/A1 (5.49%) genotypes in breast cancer patients in comparison with controls 23.40%, 14.10%, 5.77%, 1.92% respectively. However the differences were not significant. After division of the cases and controls according to the age the prevalence of the risk alleles and genotypes in women at the age 50 years or less was higher as compared to women older than 50 years. In the younger women group, the p53 BstUI polymorphism genotype frequencies were 6.2% for BstUIPro/Pro, 31.0% for BstUIArg/Pro and 62.8% for BstUIArg/Arg in controls and 11.11 %, 40.74% and 48.15% in cases respectively. The risk of disease for BstUIPro/Pro genotype was more than two-fold higher in comparison with the BstUIArg/Arg (OR=2.34, 95% CI=0.53-10.24). In p53 MspI the genotype frequencies were 1.77% for MspIA1/A1, 24.78% for MspIA1/A2 and 73.45% for MspIA2/A2 in controls and 11.11%, 18.52% and 70.37% in cases respectively. The risk of disease for MspIA1/A1 genotype was more than six-fold higher in comparison with the MspIA2/A2 (OR=6.55, 95% CI=1.02-41.98). When we evaluated the association of both polymorphisms together with the breast cancer risk we observed that the highest risk was connected with the genotype BstUIPro/Pro / MspIA1/A1 (OR=2.99, 95% CI=0.69-13.06). Our results indicate that both BstUI and MspI p53 polymormphisms might play the role in the breast cancer development especially in women younger than 50 years.