BRCA1 novel variation V1736D and in silico analysis of SNP Q356R in Sudanese patients with breast cancer

Abstract

Open Peer Review AbstractBreast cancer (BC) remains one of the leading causes of death Background: in women worldwide. The deleterious mutation has a significant role in BRCA1 developing BC, and the risk has been estimated to be 46-87%. Many studies emphasize the need for mining gene mutations that might have a role BRCA1 in BC pathogenesis and could affect early disease onset. This study was conducted to screen for possible pathogenic single nucleotide polymorphisms (SNPs) in , targeting three regions: two in exon 11 and the third in exon BRCA1 20.45 blood samples were collected from patients diagnosed with BC. Methods:DNA was extracted and selected regions were amplified by PCR using three sets of primers -two within exon 11 and one within exon 20 of . Subsets BRCA1 of 10 samples were selected for each primer set (30 PCR products) and 2018, 6:1461 Last updated: 29 JAN 2018 Discuss this article (0) Comments of 10 samples were selected for each primer set (30 PCR products) and sequenced. Sequences were analyzed using various bioinformatics tools.Two missense variations were found, Q356R (rs1799950) in one Results: patient (27 years old) and a novel SNP, V1736D, in three premenopausal patients (≤45 years), which were located within exons 11 and 20, respectively. Both detected variants were heterozygous, a status found in all patients detected with such monoallelic variation. Both missense variants underwent in analysis. The well-known variation, rs1799950, was predicted to alter the silico protein activity, conferred by a mutant residue (R-Arg), owing to the position with a bigger size and positive charge. The novel SNP, V1736D, was predicted to play a role in the pathogenesis of BC.Both variants require further investigation, firstly to assess their Conclusion: contribution to BC and secondly to determine their potential diagnostic value when assessed in a larger population. In Africa, in 2012, the rate was about 94,000 women with BC, which resulted in 48,000 deaths 3 , and studies in Africa have described a poor outcome with a late diagnosis, due to the aggressiveness of the disease and the absence of screening programs [4][5][6][7] .In Sudan, BC occurs at the highest frequency among women compared to other types of cancer [8][9][10][11][12][13] . In a hospital-based statistical report in Sudan 13 , BC was found to be the most commonly diagnosed malignant tumor and was characterized by early onset and bad prognosis. The report showed invasive ductal carcinoma to be the predominant type (82%), and 74% of patients were <50 years old with an advanced disease stage, indicating that most cases remain undiagnosed for long periods 8,9,[13][14][15] . BRCA1 (OMIM_113705) was mapped in 1994 and subsequently cloned. It is located on chromosome 17 region 2, band 1 (17q21), which is responsible for encoding 1863 amino acids 16 . Since 1995, the BRCA1 tumor suppressor protein has been found to arrest cell proliferation, play an important role in the repairing process of DNA damage, and was suggested to have a role in cel...

Significant association of BRCA1 (rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan

“…Previously, similar studies showed the association of rs1799950 (BRCA1) with Breast cancer risk. The homozygous mutant genotype was found to be associated with breast cancer risk in the Saudi population [39] while the heterozygous genotype was found to be associated with breast cancer risk in Sudanese [40]. rs1799950 genotype exhibited a positive relationship with family history, nulliparity, menstrual status, ER-and PR-status, but displayed negative correlation with HER2 abundance.…”