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INTRODUCTION AND OBJECTIVES: Endometriosis is a multifactorial gynecological disease and some advanced cases of endometriosis have an increased risk of developing epithelial ovarian cancer. Although, etiology of endometriosis is not entirely understood, it is recognized that genetic factors may contribute to development of the disease. microRNAs are a class of small non-coding RNAs that regulate post-transcriptional gene expression, influencing on various eukaryotic processes such as proliferation, differentiation, cell migration, oncogenesis. Some studies have shown that many conditions have been associated with down or up-regulation in the expression of certain microRNAs. This difference in gene expression may be explained by the occurrence of single nucleotide polymorphisms (SNPs) in microRNAs coding genes. DROSHA and DICER1 enzymes participate of the main stages of the microRNAs synthesis. Polymorphisms (rs10719 and rs3742330) can influence the stability and genes expression, and affect the binding of miRNAs. Therefore, the objective of the present study was to evaluate the association of DROSHA and DICER1 SNPs in the development of endometriosis and different conditions. MATERIAL AND METHODS: First, a case-control study was performed with 240 endometriosis cases and 242 controls. This study was approved by the Human Research Ethics Committees of HFSE (Protocol: 414/2011) and HMF (Protocol: 1.244.294/2015). DROSHA rs10719 G>A and DICER1 rs3742330 A>G SNPs were genotyped by TaqMan system and a binary logistic regression was used to evaluate the association between SNPs and endometriosis. Moreover, a literature review was performed using all published article (Pubmed database) regarding the association of the studied SNPs and different conditions, included cancer. RESULTS AND CONCLUSION: DROSHA rs10719AA was observed in 20.2% of controls, 21,9% of women with endometriosis and 21.4% of deep infiltrative endometriosis (DIE), while DICER1 rs3742330GG was only found in the women with endometriosis (2.1%) and DIE (2.5%). The frequency of the DICER1 rs3742330GG was significantly different between endometriosis cases and controls (P < 0.05), suggesting a tendency to present increased risk for endometriosis and DIE. It was observed differences in the allele’s frequencies of DROSHA rs10719A (6 - 79%) and DICER1 rs3742330G (10.2 - 55.1%) among populations. Both SNPs were risk factors for colorectal and bladder cancer. Also, DICER1 rs3742330 SNP was protective factor to precancerous cervical lesion, papillary thyroid carcinoma, hepatocellular carcinoma, gastric and prostate cancer. The results suggest that only DICER1 rs3742330 A>G SNP may be associated with susceptibility to endometriosis. Also, the frequency of both SNPs was significantly different among populations. Therefore, the study of this variant involved in gene expression regulation is important to help understand the etiopathogenesis of endometriosis and cancer.
Andre Luiz Mencalha
Parabéns pelo trabalho!
No trecho do resumo você comentou sobre “Polymorphisms (rs10719 and rs3742330) can influence the stability and genes expression, and affect the binding of miRNAs.”, poderia dizer onde ocorre esse SNP (miRNA ou mRNA, ou até mesmo nos genes das proteínas comentadas)? Lendo mais adiante eu vi que é nas proteínas. E como afeta a estabilidade, aumenta ou diminui? E porque?
Como você comparou seu dado de frequência com o da população, que programa? você considerou todos os dados ou fez uma triagem, mulheres, idade, caucasiano,....dentre outros fatores?
No trecho “DICER1 rs3742330 A>G SNP may be associated with susceptibility to endometriosis.” Como você concluiu que esse SNP é um marcador de susceptibilidade?
Obrigado
Flavia Vasconcelos
Boa tarde, Matheus
Sou Flavia Vasconcelos e vou avaliar seu pôster. Parabéns pelo trabalho. Trabalhar com amostras e dados de pacientes não é tarefa simples. Você que realizou todos os experimentos? Inclusive a análise epidemiológica e de estatísticas?
No resumo vocês sugerem que os SNPs são fatores associados à diferentes cânceres. A forma como está descrita parece que foi feito um estudo prospectivo com acompanhamento das pacientes.Entretanto, a hipótese vem da literatura.
Quais os próximos passos do estudo?
Abraços
Matheus Pereira de Mello
1. Em relação aos procedimentos, eu não fiz todos. Participei de extrações de DNA, pesquisa e revisão da bibliografia e montagem de tabelas. As análises estatísticas e epidemiológicas foram feitas pela minha orientadora.
2. Sim, não foi um estudo prospectivo. Nós fizemos uma revisão sistemática.
3. O próximo passo desse estudo seria a publicação em um periódico de relevância na comunidade científica.
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Matheus Pereira de Mello