Padrão de metilação dos genes CDH1, BRCA1, hMLH1 e polimorfismos das enzimas TS e MTHFR do ciclo do folato em tecido tumoral mamário
Data
2010-02-22
Autores
Legnaro, Chiara de Campos [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer de mama é o tipo de câncer mais comum entre as mulheres, correspondendo a 22% de todos os casos. Foram estimados mais de 1.050.000 casos novos de câncer de mama em todo o mundo no ano 2000. Mecanismos epigenéticos como a ativação e desativação de genes por meio da hipometilação e hipermetilação, respectivamente, da região promotora dos genes estão associados ao surgimento de diversos tipos de cânceres. Embora os fatores que resultam na metilação aberrante ainda não sejam bem conhecidos, a deficiência de folato têm sido associada a esse mecanismo no desenvolvimento de cânceres como de colo uterino, pulmão, mama, cólon e cérebro. Neste trabalho, foi avaliado se os polimorfismos em genes de enzimas chaves no metabolismo do folato como a timidilato sintase (TS) e metilenotetrahidrofolato redutase (MTHFR) influenciam o padrão de metilação da região promotora dos genes CDH1, BRCA1 e hMLH1 em amostras de câncer de mama. A metilação foi avaliada através da MS-PCR e os polimorfismos por PCR e PCR-RFLP. Não houve diferença estatisticamente significante (p<0.05, teste exato de Fisher) do padrão de metilação dos genes quando comparado com estádio, grau histológico, idade e freqüência dos polimorfismos. Os polimorfismos 5´UTR TS, C677T e A1298C MTHFR não influenciam no padrão de metilação da região promotora dos genes CDH1, BRCA1 e hMLH1 em amostras de câncer de mama
The breast cancer is the most frequent cancer in women equivalent to 22% of all cases. It were estimated more than 1.050.000 new cases of breast cancer in all the world in the year 2000. Epigenetic mechanisms like ativation and desativation of genes by hypomethylation and hipermethylation, respectivelly, of genes promoter regions are associated to the appearance of several types of cancer. Although the factors that result in aberrant methylation are not well known, the lack of folate has been associated to this mechanism in the development of cancers like cervical uterine, lungs, breast, colon and brain. In this research it was evaluated if the polymorphisms in genes of folate metabolism enzymes like the thymidilate syntase (TS) and methylenetetrahydrofolate reductase (MTHFR) influence the methylation pattern of the promoter of genes CDH1, BRCA1 and hMLH1 in samples the tissue of breast cancer. The methylation was evaluated through the MS-PCR and the polymorphisms through PCR and PCR-RFLP. We observed no statistically significant associations (p<0.05, exact test of Fisher) of the patterns of methylation of genes when compared to stage, histologic grade, age and frequency of polymorphisms. The polymorphisms 5´UTR TS, C677T AND A1298C MTHFR did not influence in the pattern of methylation of the promoter region of genes CDH1, BRCA1 e hMLH1 in samples the tissue of breast cancer
The breast cancer is the most frequent cancer in women equivalent to 22% of all cases. It were estimated more than 1.050.000 new cases of breast cancer in all the world in the year 2000. Epigenetic mechanisms like ativation and desativation of genes by hypomethylation and hipermethylation, respectivelly, of genes promoter regions are associated to the appearance of several types of cancer. Although the factors that result in aberrant methylation are not well known, the lack of folate has been associated to this mechanism in the development of cancers like cervical uterine, lungs, breast, colon and brain. In this research it was evaluated if the polymorphisms in genes of folate metabolism enzymes like the thymidilate syntase (TS) and methylenetetrahydrofolate reductase (MTHFR) influence the methylation pattern of the promoter of genes CDH1, BRCA1 and hMLH1 in samples the tissue of breast cancer. The methylation was evaluated through the MS-PCR and the polymorphisms through PCR and PCR-RFLP. We observed no statistically significant associations (p<0.05, exact test of Fisher) of the patterns of methylation of genes when compared to stage, histologic grade, age and frequency of polymorphisms. The polymorphisms 5´UTR TS, C677T AND A1298C MTHFR did not influence in the pattern of methylation of the promoter region of genes CDH1, BRCA1 e hMLH1 in samples the tissue of breast cancer
Descrição
Palavras-chave
Ciências médicas, Mamas - Cancer, Polimorfismo (Genetica), Methylation, Suppressor genes
Como citar
LEGNARO, Chiara de Campos. Padrão de metilação dos genes CDH1, BRCA1, hMLH1 e polimorfismos das enzimas TS e MTHFR do ciclo do folato em tecido tumoral mamário. 2010. 52 f. Dissertação (mestrado) - Universidade Estadual Paulista, Faculdade de Medicina de Botucatu, 2010.