Identification and frequency of the rs12516 and rs8176318 BRCA1 gene polymorphisms among different populations

Abstract

Abstract. Genetic mutation of breast cancer 1 (BRCA1) is one of the most notable factors responsible for a proportion of breast cancer cases. BRCA1 encodes a 1,863-amino acid protein and functions as a negative regulator of tumor growth. Thus, investigation of the underlying mechanisms that regulate BRCA1 gene expression provide further insight into possible targets for breast cancer therapy. Previous studies have demonstrated that the genetic variants in the BRCA1 3' untranslated region (3'UTR), in addition to the cytosine-phosphate-guanine (CpG) islands in the promoter region, are significantly associated with breast cancer risk; however, the role of single nucleotide polymorphisms (SNPs) in the BRCA1 3'UTR remains unclear. The present study aimed to investigate the association between SNPs and BRCA1 mRNA expression levels. Bioinformatics analysis demonstrated that 2 SNPs in the BRCA1 3'UTR (rs12516 and rs8176318 with putative microRNA binding sites) were significantly correlated with mRNA expression in lymphoblastoid cell lines (P=2.55x10 , respectively). Furthermore, the genotype frequency distribution varied between populations worldwide. In addition, 3 CpG islands and several transcription factor binding sites in the BRCA1 promoter region were established. The identification of such polymorphisms and CpG islands may aid in designing improved therapeutic strategies to treat patients with BRCA1-associated breast cancer.

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

“…Herein, the frequencies of the GG (31.33%), GT (52.0%), and TT (16.67%) genotypes in the patients were comparable to those of the GIH (29.5%, 52.3%, and 18.2%, respectively). Our G (57.3%) and T (42.6%) allele frequencies were comparable to those of the GIH (55.7% and 44.3%) and CHD (56.5% and 44.5%) [15]. Previously, a study of African-American women reported that the rs3092995 in the 3′-UTRs of the BRCA1 increased the risk of BC [16].…”

“…Other studies have reported that different alleles, rs12516 and rs8176318, increased the risk of BC [17]. The rs8176318 G/T variant was linked with increased risk of BC in studies across different populations worldwide [15]. The rs8176318 has also been reported to be a risk factor in African-American women, with an OR of 12.19 [18].…”

Identification of Variants (rs11571707, rs144848, and rs11571769) in the BRCA2 Gene Associated with Hereditary Breast Cancer in Indigenous Populations of the Brazilian Amazon

“…Regarding the seven SNPs of the BRCA2 gene, there is an association of the development of BC with the rs115771651, rs766173, and rs1799943 variants in the Asian population [ 28 , 29 ] and rs1799944 and rs1799943 polymorphism in Caucasians [ 30 , 31 ]. The other three polymorphisms (rs11571707, rs11571769, rs144848) of the BRCA2 gene evaluated here are related to hereditary breast cancer [ 32 , 33 ].…”

Genetic variants in microRNA‐binding sites of DNA repair genes as predictors of recurrence in patients with squamous cell carcinoma of the oropharynx

“…Recently, BRCA1 rs12516 has been shown to have several potential miRNAs for binding. Bioinformatics analysis and SNP function prediction demonstrated that the site of BRCA1 rs12516 C‐to‐T transition had six potential binding miRNAs: hsa‐miR‐188–5p, hsa‐miR‐502–5p, hsa‐miR‐557, hsa‐miR‐623, hsa‐miR‐637, and hsa‐miR‐639 . Among these miRNAs, miRNA‐188 was downregulated in oral squamous cell carcinoma and inhibited proliferation and invasion by targeting SIX1 .…”

“…rs12516 C-to-T transition had six potential binding miRNAs: hsa-miR-188-5p, hsa-miR-502-5p, hsa-miR-557, hsa-miR-623, hsa-miR-637, and hsa-miR-639. 28 Among these miRNAs, miRNA-188 was downregulated in oral squamous cell carcinoma and inhibited proliferation and invasion by targeting SIX1. 29 Similar functions of miRNA-188 were found in other types of cancer, including prostate cancer, hepatocellular carcinoma, and acute myeloid leukemia.…”