Análise de polimorfismos associados à fissura do lábio e/ou palato não sindrômica como marcadores de susceptibilidade para os cânceres de boca e de mama

Abstract

Epidemiological studies have shown a relationship between cancer and oral fissure, mainly due to the similarities of genetic factors. To better understand this relationship, this casecontrol study evaluated polymorphisms in genes associated with nonsyndromic oral clefts in patients with oral and breast cancer. The samples were collected in two hospitals: an in the southeastern region of Brazil (Santa Casa de Montes Claros, Montes Claros, Minas Gerais) and the other in the Northeastern region of Brazil (Liga Contra o Cancer, Natal, Rio Grande do Norte). For the oral cancer group 79 patients with oral squamous cell carcinoma (OSCC) and 130 controls (OSCC-Control), and for the breast cancer, 159 patients with breast cancer (BC) and 121 controls (BC-Control) were included. Five single nucleotide polymorphisms (SNPs) in the IRF6 genes (rs642961), WNT3A (rs708111), GSK3β (rs9879992), 8q24 (rs987525), WNT11 (rs1533767), representing regions associated with oral cleft, were selected. The study groups were adjusted by covariates using multivariate logistic regression analysis using the package SNPassoc in R software. For the analysis of the SNP-SNP interaction, the package mbmdr in R software (n=1,000) for false-positive correction and values of p<0.05 were considered significant. The results shows that the variate G allele of rs9879992 in GSK3β was significantly associated with oral cancer risk (p=0.02), whereas A allele rs1533767 in WNT11 showed a protective effect against it (p=0.04). No individual SNP was associated with breast cancer. Several SNP-SNP interactions principally containing SNPs in WNT3A, GSK3β and WNT11 were associated with oral and breast cancer. These results reveal associations between SNPs in GSK3β and WNT11 with oral cancer risk, and multiple SNP-SNP interactions involving IRF6, WNT3A, GSK3β, 8q24 and WNT11 in the risk of both oral and breast cancer. Studies in larger populations are important for a better understanding of the epistatic interactions of this group of genes studied.