Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba

Abstract

Basal Cell Carcinoma (BCC) is a cutaneous neoplasm characterized by the presence of cancer cells, which originate from the cells of the epidermis, preventing cell differentiation and affecting the cutaneous attachments. Its main development factor is exposure to solar radiation, causing DNA damage. In response to the damage, repair mechanisms such as the mismatch repair mechanism (MMR) are used to maintain genomic integrity. The presence of single nucleotide polymorphism (SNP) in MMR genes can promote changes in the activity of its gene product, leading to tumor progression and câncer. The present study analyzed the SNPs rs63751445 (A> G) and rs63751089 (T> C) in the MSH2 gene and rs863224614 (T> G) in the MSH6 gene, in 100 paraffin tissue samples from patients diagnosed with CBC in Paraíba. The results of the analyzes were obtained by the genotyping method Didesoxi Single Allele Specific PCR - DSASP. Bioestat software was used for the statistical analyzes, which consisted of Chi-square and Fisher Exact tests, with a significance level of 5%. Molecular anchoring tests (Docking) were performed in the Hex 8.0.0 software, for analyzes of the complexes, with the Pymol and the software WinCoot 0.8.4 was used. The observed and expected genotype frequency relation in the SNPs rs63751445, rs63751089 in the MSH2 gene and the rs863224614 SNP in the MSH6 gene indicate Hardy-Weinberg imbalance with X² = 100 and p-value <0.0001 associated with susceptibility to Basal Cell Carcinoma. The anchoring allowed to identify important interactions, wherein the substitution of Phenylalanine for Leucine the interaction with DG24 is lost, suggesting the compromise of the protein function. With a statistically significant association with susceptibility to the risk of developing BCC, the results obtained may be used as molecular marker potentials.