Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer
| Autor: | Idalia Garza-Veloz, María Marisela Sánchez-Chaparro, Omar Alejandro Zayas-Villanueva, Diana Reséndez-Pérez, Margarita L Martinez-Fierro, Laura Elia Martínez-de-Villarreal, Iram P. Rodriguez-Sanchez, Mayra A. Gómez-Govea, Ivan Delgado-Enciso |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system diseases Clinical Biochemistry MiRNA binding Biology hereditary breast and ovarian cancer Article polymorphism 03 medical and health sciences 0302 clinical medicine Polymorphism (computer science) microRNA 3’UTR region Allele skin and connective tissue diseases Gene miRNA Genetics lcsh:R5-920 Three prime untranslated region Odds ratio BRCA1 BRCA2 female genital diseases and pregnancy complications 030104 developmental biology 030220 oncology & carcinogenesis Population study lcsh:Medicine (General) |
| Zdroj: | Diagnostics Diagnostics, Vol 10, Iss 298, p 298 (2020) Volume 10 Issue 5 |
| ISSN: | 2075-4418 |
| Popis: | Hereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the BRCA1 and BRCA2 genes. The 3&rsquo UTR region allows for the binding of microRNAs, which are involved in genetic tune regulation. We aimed to identify allelic variants on 3&rsquo UTR miRNA-binding sites in the BRCA1 and BRCA2 genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3&rsquo UTR regions of BRCA1 and BRCA2 were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3&rsquo UTR, namely: four in BRCA1 (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in BRCA2 (rs15869 (A/C), rs7334543 (A/G), rs1157836 (A/G), and rs75353978 (TT/del TT)). A new variant in position c.*457 (A/C) on 3&rsquo UTR of BRCA2 was also identified. The following three variants increased the risk of HBOC in the study population: rs111791349-A, rs15869-C, and c.*457-C (odds ratio (OR) range 3.7&ndash 15.4 p < 0.05). Genetic variants into the 3&rsquo UTR of BRCA1 and BRCA2 increased the risk of HBOC between 3.7&ndash 15.4 times in the study population. The presence/absence of these polymorphisms may influence the loss/creation of miRNA binding sites, such as hsa-miR-1248 in BRCA1 3&prime UTR or the hsa-miR-548 family binding site in BRCA2. Our results add new evidence of miRNA participation in the pathogenesis of HBOC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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