Abstract 216: Association of p53 codon 72 polymorphism and colorectal cancer risk

Abstract

Abstract Background: Colorectal cancer (CRC) is a complex, multistep and mutifactorial process, thought to be resulted from an interaction between environmental and genetic factors. Mutation of the TP53 tumor suppressor gene, an important mediator against genotoxic insults, is considered one of the most common genetic change in CRC, suggested to represent a suitable candidate for a CRC susceptibility locus. Single nucleotide polymorphisms (SNP) have been widely reported to influence the risk of cancers. The p53 codon 72 SNP leads to a proline to arginine substitution. Several evidences suggest that these variants confer different properties to the p53 protein, indicating that they are not biochemically equivalent, as they have different capacities for inducing target gene transcription, physically interacting with others proteins or modulating the apoptosis. Many studies have evaluated the association between this SNP and CRC, however, results were inconsistent, performed on populations with different genotype frequencies, and different environmental and epidemiological characteristics. Objective: The aim of this study was to evaluate the correlation of this SNP with clinicopathological variables in Brazilian CRC patients. Material and Methods: 101 non-related patients with CRC were evaluated (52 women and 49 men). DNA was isolated from frozen tumor tissue using phenol/chloroform protocol. The SNP was evaluated by Sanger sequencing analysis. The relationships between the SNP and the clinicopathological variables were analyzed by the qui-square test (SPSS 17.0). Results: The p53 codon 72 SNP was significantly associated with gender (p = 0.026), recurrence (p = 0.004), durty tumor necrosis (p = 0.013) and pathological T staging (p = 0.045), suggesting that the presence of at least one Pro72 allele and/or the absence of at least one Arg72 allele are associated with worst prognosis, in agreement with studies that showed that the Pro72 allele is less efficient than Arg72 allele at suppressing cell transformation and inducing apoptosis. The allele frequency of p53 Pro72 was 0.26, almost the same in European populations, consistently with the colonization origin of Brazil and with the latitude-dependent distribution of the genotypes, based on the observations that the difference of p53 codon 72 alleles is tightly associated with the variation of temperature. These findings indicate that this SNP is associated with CRC in this population. However, it is not possible to rule out the possibility that other factors, such as lifestyle and dietary, might impact the association of this SNP with CRC. Conclusion: These results suggest that p53 codon 72 SNP may play a role in CRC developing and progression, thus confering a possible genetic risk factor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 216. doi:10.1158/1538-7445.AM2011-216