Made available in DSpace on 2014-12-17T15:32:28Z (GMT). No. of bitstreams: 1 Tese_GeorgeJFN.pdf: 2720479 bytes, checksum: 6d72db8b12a0e5f743d69a67430d66b7 (MD5) Previous issue date: 2010-02-18 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) modulate important functions strictly related to the development, invasion and metastasis of several human cancers among them the squamous cell carcinoma of the tongue (SCCT). However, individual genetic factors such as the functional single nucleotide polymorphisms (SNPs) influence the pattern of protein expression of these MMPs and thus may be related to the variability observed in the clinical behavior of patients with SCCT. In this context, the present cross-sectional study aimed to evaluate the association between the frequency of the functional SNPs MMP-7 -181 A/G and MMP-9 -1562 C/T and the clinical (age, gender and metastasis) and pathological (malignancy histological grading and immunohistochemistry expression) features of SCCT cases. Genotyping of these SNPs were performed by PCR-RFLP on DNA samples from 71 cases of SCCT and 60 individuals without cancer who constitute the control group. Among the results of this research, it was observed that the frequency of the polymorphic alleles MMP-7 -181 G and MMP-9 -1562 T in SCCT patients was 28% and 12%, respectively, and the frequency of the heterozygotes A/G (PR = 2.00; p < 0.001) and C/T (PR = 1.54; p = 0.014) were significantly higher in the patient group than in the controls. The prevalence of patients carrying the combination of SNPs studied was significantly associated with SCCT cases (PR = 2.00; p = 0.011) and metastasis (PR = 2.00; p < 0.001). Furthermore, with the frequency of SNPs analyzed, the age, gender, histological grading and immunoreactivity of MMP-7 and MMP-9 formed clinical and pathological parameters relevant to the identification of population subgroups more related to the development of SCCT and metastasis. Based on these results, it is suggested that the protein expression levels of MMP-7 and -9 substantially influence the balance between their pro- and anticancer biological functions and hence the clinicopathological profile of the squamous cell carcinoma of the tongue / As metaloproteinases da matriz extracelular-7 (MMP-7) e -9 (MMP-9) modulam importantes fun??es relacionadas ao desenvolvimento, invas?o e met?stase de diversos c?nceres humanos, dentre os quais o carcinoma epiderm?ide de l?ngua (CEL). Entretanto, fatores gen?ticos individuais, tais como polimorfismos de nucleot?deo ?nico (SNPs) funcionais, influenciam no padr?o de express?o proteica dessas MMPs, podendo estar relacionados ? variabilidade no comportamento cl?nico tumoral observado em pacientes com CEL. Neste contexto, o presente trabalho objetivou, atrav?s de an?lise em sec??o transversal, estudar a associa??o entre a frequ?ncia dos SNPs funcionais MMP-7 -181 A/G e MMP-9 -1562 C/T e as caracter?sticas cl?nicas (idade, sexo e met?stase) e patol?gicas (grada??o histol?gica e express?o imuno-histoqu?mica) em uma s?rie de casos de CEL. A genotipagem dos referidos SNPs foi executada por PCR-RFLP em amostras de DNA de 71 casos de CEL e de 60 indiv?duos sem c?ncer, que constitu?ram o grupo controle. Dentre os resultados da presente pesquisa, evidenciou-se que a frequ?ncia dos alelos polim?rficos MMP-7 -181 G e MMP-9 -1562 T nos pacientes com CEL foi de 28% e 12%, respectivamente, sendo as frequ?ncias dos heterozigotos A/G (RP = 2.00; p < 0.001) e C/T (RP = 1.54; p = 0.014) significativamente maiores neste grupo de pacientes que no grupo controle. A preval?ncia dos pacientes portadores da combina??o dos SNPs estudados associou-se significativamente aos casos de CEL (RP = 2.00; p = 0.011) e ? met?stase (RP = 2.00; p < 0.001). Ademais, junto ? frequ?ncia dos SNPs analisados, a idade, sexo, grada??o histol?gica e imunoexpress?o da MMP-7 e -9 constitu?ram par?metros clinicopatol?gicos relevantes para a identifica??o de subgrupos populacionais mais predispostos ao desenvolvimento do CEL e met?stase. Frente a estes resultados, sugere-se que os n?veis de express?o da MMP-7 e -9 influenciam consideravelmente no balan?o entre suas fun??es pr? e antineopl?sicas e, consequentemente, no perfil clinicopatol?gico do carcinoma epiderm?ide de l?ngua.