Dataset Information

Effect of variation in miRNA-binding site (rs8176318) of the BRCA1 gene in breast cancer patients

ABSTRACT: Background/aim:A variation in the 3 prime untranslated regions (3?-UTRs) affects the binding of microRNA (miRNA) to the breast cancer (BC) susceptibility gene 1 (BRCA1) gene, and thus regulate its expression. In this study, the consequences of a variation in the miRNA-binding site (rs8176318G>T) in the 3?-UTRs of BRCA1 and its association with the risk of BC were investigated. Materials and methods:The selected variation (rs8176318G>T) was genotyped in BC patients (n = 300) and healthy controls (n = 300) using allele-specific polymerase chain reaction (PCR) [tetra-primer amplification refractory mutation system-PCR (T-ARMS-PCR)]. The results of the T-ARMS-PCR were further confirmed by Sanger sequencing through a random selection of 10% previously analyzed samples by T-ARMS-PCR. Association of this variation with BC was tested by calculating the odds ratio (OR) (at 95% CI) and ?2-value using 4 different genetic models (codominant, dominant, recessive, and additive models). Results:Using Fisher’s exact test, a significant association between variant rs8176318 (G>T) and BC was found in codominant [?2-value = 15.68, df: 2 P < 0.0004], dominant [OR = 1.557 (1.082–2.241), P <0.0213], recessive [OR = 0.474 (0.3204–0.7017), P = 0.0002] and additive models [OR = 1.609 (1.282–2.018), P < 0.0001]. Conclusion:It was therefore concluded that there is a significant association between rs8176318 and BC risk in a case-control study in a Pakistani population. Furthermore, an association study using a large sample size is required to further verify these findings.

SUBMITTER: Ahmad M

PROVIDER: S-EPMC7018252 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Effect of variation in miRNA-binding site (rs8176318) of the BRCA1 gene in breast cancer patients

Ahmad Mushtaq M Ahmad Mushtaq M Jalil Fazal F Jalil Fazal F Haq Mutiul M Shah Aftab Ali

Turkish journal of medical sciences 20191024 5

<h4>Background/aim</h4>A variation in the 3 prime untranslated regions (3′-UTRs) affects the binding of microRNA (miRNA) to the breast cancer (BC) susceptibility gene 1 (BRCA1) gene, and thus regulate its expression. In this study, the consequences of a variation in the miRNA-binding site (rs8176318G>T) in the 3′-UTRs of BRCA1 and its association with the risk of BC were investigated.<h4>Materials and methods</h4>The selected variation (rs8176318G>T) was genotyped in BC patients (n = 300) and he ...[more]

PMID: 31651107

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Project description:UNLABELLED:Multiple lines of evidence suggest regulatory variation to play an important role in phenotypic evolution and disease development, but few regulatory polymorphisms have been characterized genetically and molecularly. Recent technological advances have made it possible to identify bona fide regulatory sequences experimentally on a genome-wide scale and opened the window for the biological interrogation of germ-line polymorphisms within these sequences. In this study, through a forward genetic analysis of bona fide p53 binding sites identified by a genome-wide chromatin immunoprecipitation and sequence analysis, we discovered a SNP (rs1860746) within the motif sequence of a p53 binding site where p53 can function as a regulator of transcription. We found that the minor allele (T) binds p53 poorly and has low transcriptional regulation activity as compared to the major allele (G). Significantly, the homozygosity of the minor allele was found to be associated with an increased risk of ER negative breast cancer (OR = 1.47, P = 0.038) from the analysis of five independent breast cancer samples of European origin consisting of 6,127 breast cancer patients and 5,197 controls. rs1860746 resides in the third intron of the PRKAG2 gene that encodes the ? subunit of the AMPK protein, a major sensor of metabolic stress and a modulator of p53 action. However, this gene does not appear to be regulated by p53 in lymphoblastoid cell lines nor in a cancer cell line. These results suggest that either the rs1860746 locus regulates another gene through distant interactions, or that this locus is in linkage disequilibrium with a second causal mutation. This study shows the feasibility of using genomic scale molecular data to uncover disease associated SNPs, but underscores the complexity of determining the function of regulatory variants in human populations. ELECTRONIC SUPPLEMENTARY MATERIAL:The online version of this article (doi:10.1007/s11568-010-9138-x) contains supplementary material, which is available to authorized users.

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Effect of variation in miRNA-binding site (rs8176318) of the BRCA1 gene in breast cancer patients

Publications

Effect of variation in miRNA-binding site (rs8176318) of the BRCA1 gene in breast cancer patients

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