TP53 Codon 72 Heterozygosity May Promote MicrosatelliteInstability In Sporadic Colorectal Cancer

Document Type : Original Article


1 Anatomy Department, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Biotechnology Department, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran


Objective: The polymorphic variants at codon 72 of the p53 gene, encoding proline or arginine at residue 72, produce marked changes in the p53 structure. From the evidence that the DNA mismatch repair system and p53 interact to maintain genomic integrity, we hypothesized that codon 72 variations may influence the prevalence of microsatellite instability (MSI), a feature of malignancies associated with mismatch repair deficiency in sporadic colorectal cancer. 
Materials and Methods: We investigated the frequency of MSI in three P53 codon 72 genotypes using genomic DNAs from 144 paraffin blocks of sporadic colorectal adenocarcinomas by testing the BAT-26 poly(A) marker. We used PCR-SSCP analysis to detect tumor sample MSI for the nonisotopic detection of deletions in the BAT26 poly (A) mononucleotide repeat. Associations between qualitative variables were 
evaluated using the χ2-test. Statistical significance level was set to p ≤ 0.05.

Results: MSI analysis revealed that 24.3% of the tumors (n=35) were MSI-positive and 75.7% (n=109) were MSI-negative. The frequency of microsatellite instability in the arginine/arginine, arginine/proline and proline/proline genotypes were 11 (16.9%), 22 (36.1%) and 2 (11.1%) respectively. A significant difference in distribution of MSI was found for the arginine/proline genotype compared with the grouped arginine/arginine and proline/proline genotypes (p=0.05). 

Conclusion: Our findings suggested that colorectal adenocarcinomas arising in individuals with the p53 codon 72 arginine/proline heterozygosity are more prone to microsatellite instability than those with other p53 genotypes. In our study, MSI was important in the carcinogenesis of sporadic colorectal cancer arising in pro/arg heterozygotes.