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 χ 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 [χ 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.

SNPs in miRNAs and Target Sequences: Role in Cancer and Diabetes

“…BRCA is one of the well-studied genes associated with BC. This gene has a highly conserved 3′UTR of 1381 nucleotides encodes a 1863 amino acid protein and functions as a tumor suppressor gene that regulates various cellular processes including cell cycle checkpoint control, chromatin remodeling, DNA repair, regulation of transcription, protein ubiquitination, and apoptosis ( Yang et al, 2016 ; Ahmad et al, 2019 ). The 3′UTR region of the BRCA1 gene plays a pivotal role in the localization, stability, and mRNA transport.…”

“…SNPs in 3′UTR of this gene might alter genes expression and therefore increase the risk of BC. The prevalence of SNPs in 3′UTR of BRCA1 modulating the miRNA binding site that can emerge as a significant biomarker of the disease ( Ahmad et al, 2019 ).…”

“…rs8176318 is located at the region where miR-639 is assumed to bind. Enhanced risk of BC was reported in individuals with GT or GG compared to TT genotype in the Pakistani population ( Ahmad et al, 2019 ). This SNP is also associated with the risk of TNBC and ovarian cancer in an Irish population.…”