No Evidence for the Pathogenicity of the BRCA2 c.6937 + 594T>G Deep Intronic Variant: A Case–Control Analysis
| Autor: | Rafael Rivera-Lugo, Miguel Echenique, Lenin Godoy, Elinette Albino, Luis Negrón, Julie Dutil, Alvaro N.A. Monteiro, Jaime Matta, Nelly Arroyo |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
BRCA2 Protein
0301 basic medicine Genetics Genes BRCA2 Genetic Variation Breast Neoplasms Original Articles General Medicine Prom Biology Pathogenicity Introns female genital diseases and pregnancy complications 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Case-Control Studies 030220 oncology & carcinogenesis Case control analysis Humans Genetic Predisposition to Disease Hereditary Cancer Genetics (clinical) |
| Zdroj: | Genetic Testing and Molecular Biomarkers. 22:85-89 |
| ISSN: | 1945-0257 1945-0265 |
| DOI: | 10.1089/gtmb.2017.0187 |
| Popis: | The role of deep intronic variants in hereditary cancer susceptibility has been largely understudied. Previously, the BRCA2 c.6937 + 594TG variant has been shown to preferentially promote the inclusion of a 95 nucleotide cryptic exon and to introduce a premature termination codon. Our objective was to further assess the pathogenicity of the BRCA2 c.6937 + 594TG deep intronic variant.We examined the association between BRCA2 c.6937 + 594TG and breast cancer (BC) risk in 464 BC cases and 497 noncancer controls from Puerto Rico.The overall frequency of the G allele was 2.1% in this population. There was no association between the TG/GG genotypes and BC risk in the uncorrected model and after correcting for confounders. There was only one carrier of the GG genotype. This individual did not have personal or family history of cancer and did not meet the National Comprehensive Cancer Network criteria for hereditary cancer genetic testing.Although previous work has demonstrated that the BRCA2 c.6937 + 594TG variant affects splicing, this association study does not support a pathogenic role for the BRCA2 c.6937 + 594TG intronic variant in breast and ovarian cancer syndrome susceptibility. Furthermore, it emphasizes the need to take into account multiple diverse populations in association studies for the assessment of variant pathogenicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|