Investigating of variations in BRCA1 gene in Iranian families with breast cancer

Abstract

Background: Breast cancer is one of the most common cancers among Iranian women whose relationship with mutation status in BRCA1 is previously approved. Therefore, screening of the most mutated exons in BRCA1 in hereditary breast cancer patients provides beneficial information about the main disease-causing reason. Methods: A total of 14 Iranian hereditary breast cancer patients participated in this case series study. DNA was extracted from patients’ blood samples for PCR assay. The quality of PCR products was determined using horizontal electrophoresis. Then, sequencing and analysis of the sequencing results were performed to investigate variation status in the sequences. Results: Five variants in 4 patients were found, including 1 pathogenic variant in exon 16 (H1686Q, NM_007294.3:c.5058T>A) and 4 novel intronic variants of uncertain significance (NC_000017.11:41228314G>T, NC_000017.11:41228309C>T, NC_000017.11:41228317G>T, and NC_000017.11:41203042G>A) in BRCA1. This study was the first to report 1 rare pathogenic variant in BRCA1 (H1686Q, NM_007294.3: c.5058T>A) in an Iranian family as the main disease-causing reason. Another interesting finding was non-existence of variations in almost all globally-reported and mutated exons in BRCA1. Conclusion: Investigation of these exons in BRCA1 showed the uniqueness of mutation pattern in Iranian breast cancer patients compared to other world regions. Due to the existence of other BRCA1 exons and also other predisposing genes in breast cancer, the main cause of cancer development in other participants might have been put in those exons and genes. We concluded that the most mutated exons in BRCA1 in Iranian population may not be the same as those found in other parts of the world.

Peripubertal Nutritional Prevention of Cancer-Associated Gene Expression and Phenotypes

“…However, from a prevention standpoint, upregulation of WT-p53 in a precancerous cell could result in apoptotic destruction of the cell before full cancer cell transformation could occur. BRCA2 is well known for its impact on BC, with its heritable mutation to either BRCA1 or BRCA2 being responsible for up to 10% of all BC cases in Western countries [50,51]. Much of the current body of research on BRCA2 is associated with its loss, but lower expression levels are associated with decreased ability to repair DNA double-strand breaks, as well as an increased risk of developing BC [50,52].…”

“…BRCA2 is well known for its impact on BC, with its heritable mutation to either BRCA1 or BRCA2 being responsible for up to 10% of all BC cases in Western countries [50,51]. Much of the current body of research on BRCA2 is associated with its loss, but lower expression levels are associated with decreased ability to repair DNA double-strand breaks, as well as an increased risk of developing BC [50,52]. In the context of our study, these three upregulated tumor suppressors have well documented anticancer effects, and it is likely that their increase in expression is responsible in part for the more favorable tumor characteristics we observed.…”

Volatile Organic Compounds Analysis as a Potential Novel Screening Tool for Breast Cancer: A Systematic Review

“…Mutations in either of these genes increase the lifetime risk of BC up to 60% to 85%. 9 Yet, only 10% of all BC cases are ascribed to the involvement of hereditary factors. 10…”

Mir-153-3p Modulates the Breast Cancer Cells’ Chemosensitivity to Doxorubicin by Targeting KIF20A

“…These mutations can lead to the formation of abnormal cells that divide uncontrollably and accumulate to form a tumor. The most commonly mutated genes in breast cancer include TP53 , BRCA1 , and BRCA2 [ 1 , 2 ]. Hormonal factors also play a role in the development of breast cancer.…”