Prevalence of the BRCA1 c.68_69delAG (BIC: 185delAG) mutation in women with breast cancer from north-central Poland and a review of the literature on other regions of the country

Abstract

Aim of the studyGermline mutations in BRCA tumor suppressor genes are strongly associated with breast and ovarian cancer. The lifetime risk of these cancers in women with BRCA1 mutation is 84% and 27%, respectively.Studies on the prevalence of BRCA1 c.68_69delAG congenital mutation, the most frequent in Ashkenazi Jews, among women with breast cancer from north-central Poland and review of the literature on other regions of the country. Evaluation of the c.68_69delAG association with breast cancer risk, with respect to women's age at diagnosis and family history of cancer.Material and methods252 women with breast cancer, without any of the mutations c.5266dupC, c.181T > G, or c.4034delA, regardless of histological type and family history of cancer. The mutation was detected using allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) assay and confirmed by sequence analysis.ResultsThe c.68_69delAG mutation was disclosed in one out of the 252 women (0.4%), who had been diagnosed with breast cancer at age 43. Family investigations revealed the presence of c.68_69delAG also in the patient's mother, diagnosed with breast cancer at age 68. Sequence analysis confirmed the heterozygous status of the mutation, and family investigation its hereditary character. In the group of families with breast cancer history 1.4% frequency of c.68_69delAG was shown.ConclusionsAmong families with breast cancer aggregation, originating from north-central Poland, c.68_69delAG is a rare BRCA1 alteration, similarly to other central regions of the country, investigated by other authors. However, in northern, north-western and south-western parts of Poland, it occurs 2–4 times more frequently than in our region.

Absence of Germline BRCA1 c.68_69delAG and c.5266dupC Mutations among Hormone Receptor-negative Breast Cancer Patients: A First Impression at a Tertiary Cancer-care Facility in Tanzania

“…Similarly, a study from north-central Poland reported that the c.68_69delAG mutation was rare in their population, detected only in one out of 252 BC patients screened. Consequently, Hartwig et al (2013) recommended that the c.68_69delAG mutation should not be part of the primary BRCA1 screening test in the population of north-central Poland.…”

“…The common germline mutations within this gene are the c.68_69delAG (185delAG) located in exon 2 and the c.5266dupC (5382insC) located in exon 20. The two germline mutations were first described as founder mutations in Ashkenazi Jews (Roa et al 1996), though they are also reported in other ethnic groups in Europe (Hartwig et al 2013, Pogoda et al 2020), Asia (Chakraborty et al 2013, America (Ewald et al 2011, Rummel et al 2017), and Northern Africa (Abdel-Mohsen et al 2016, Abou-El-Naga et al 2018, Mahfoudh et al 2019. Individuals harboring these mutations are at elevated risks of BC, OC, prostate cancer, and other cancers (Barrios et al 2017).…”

“…The c.68_69delAG is described as among the two Ashkenazi BRCA1 founder mutations. This is a frameshift mutation that involves deletion of adenine and guanine at position 185 of exon 2 resulting to the creation of a stop codon, hence a premature termination of translation and truncated protein occurs (Hartwig et al 2013). The c.5266dupC, being the second BRCA1 Ashkenazi founder mutation, is also a frameshift mutation in which there is an insertion of a cytosine at position 5382 of exon 20, resulting in the production of premature truncated nonfunctioning protein (Mogahed et al 2020).…”

Mutation in Exon2 of BRCA1 Gene in Adult Bengali Bangladeshi Female Patients with Breast Cancer: An Experience from Two Tertiary-Care Hospitals

“…BRCA1 breast cancer susceptibility protein is used by the cell in an enzymatic pathway which repairs DNA molecules that have double stranded breaks (National Center for Biotechnology Information [NCBI], 2018). Besides DNA repair, it is involved in cell cycle control and regulation of apoptosis (Hartwig et al, 2013). Exon2 is one of the most common mutation sites in BRCA1 gene for c.68-69delAG (BIC: 185delAG) frameshift mutation which occurs in codon 23 of exon2, that results in the creation of stop codon which leads to premature termination of translation and significant truncation of protein, and is associated with the severity of the disease like early onset, bilaterality of breast cancer (Hartwig et al, 2013;Chakraborty et al, 2015).…”

“…Besides DNA repair, it is involved in cell cycle control and regulation of apoptosis (Hartwig et al, 2013). Exon2 is one of the most common mutation sites in BRCA1 gene for c.68-69delAG (BIC: 185delAG) frameshift mutation which occurs in codon 23 of exon2, that results in the creation of stop codon which leads to premature termination of translation and significant truncation of protein, and is associated with the severity of the disease like early onset, bilaterality of breast cancer (Hartwig et al, 2013;Chakraborty et al, 2015). The majority of breast cancers occur before age fifty (50) in most South Asian countries and it is supposed to cause by protein truncating mutations (nonsense mutation) in BRCA (Hopper et al, 1999;Liede and Narod 2002).…”