Low Prevalence of the Four Common Colombian Founder Mutations in BRCA1 and BRCA2 in Early-Onset and Familial Afro-Colombian Patients with Breast Cancer

Abstract

Background Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. In Colombian Hispanic families, four common BRCA1/2 founder mutations have previously been identified. Because nothing is known about the contribution of BRCA1/2 germline mutations to early‐onset and hereditary breast and/or ovarian cancer in Afro‐Colombians, we conducted the first study on 60 patients with early‐onset and familial breast cancer in this population. Materials and Methods Screening for the four Colombian founder mutations BRCA1/c.3331_3334delCAAG, BRCA1/c.5123C>A, BRCA2/c.2806_2809delAAAC, and BRCA2/c.1763_1766delATAA was performed using mismatch polymerase chain reaction (PCR) analysis, PCR‐based restriction fragment length polymorphism analysis, and qualitative real‐time PCR. Mutations were confirmed by direct DNA sequencing. Results The BRCA1 founder mutation c.5123C>A was identified in one family with breast and ovarian cancer (1/60, 1.7%). Three women were diagnosed with breast cancer, including one with bilateral disease, at the ages of 30, 30/33, and 52 years, and one woman was diagnosed with ovarian cancer at the age of 60 years. Conclusion Our data showed a low prevalence of the BRCA1/2 founder mutations in Colombians of African descent, implying that these mutations should not be recommended for genetic screening programs in the Afro‐Colombian population. Implications for Practice Risk reduction intervention programs are needed for women who are found to carry a BRCA1/2 mutation, as is the implementation of prevention programs for patients with inherited breast cancer, to reduce the burden of inherited diseases. With the aim of reducing racial disparities in breast cancer prevention, this study focused on genetic testing and treatment for patients in a minority population with BRCA1/2 mutations.

Prevalence ofBRCA1andBRCA2Germline Mutations in Patients of African Descent with Early-Onset and Familial Colombian Breast Cancer

“…Three patients had been diagnosed with BC before 35 years of age (5%); 48 belonged to families with at least 2 BC cases (80%) and 9 to families with both breast and OC (15%). The median ages of disease onset differed between BRCA1/2 carriers ( n = 5, including the previously identified BRCA1 _c.5123C>A carrier) 15 and noncarriers ( n = 55; 40 years, range 30-45 vs 51 years, range 33-70 years, P = .019 by Wilcoxon rank-sum test).…”

“…All Afro-Colombian families affected by breast/OC who were investigated in this study have previously been described. 15 In summary, a total of 60 families comprising 51 affected by BC and 9 affected by both breast and OC were recruited at the Cancer Leagues in Cartagena, Quibdó, and San Andres Island, Colombia, from March to December 2016. Of the 60 index patients, 52 were Afro-Colombians and 8 were Raizales.…”

“…All patients had previously been screened for the 4 Colombian BRCA1/2 founder mutations ( BRCA1 /c.3331_3334delCAAG, BRCA1 _c.5123C>A, BRCA2/ c.1763_1766delATAA, and BRCA2 /c.2808_2811delACAA) and a mutation carrier ( BRCA1 _c.5123C>A) was identified. 15 All patients were selected for genetic BRCA1/2 testing using NGS. They were classified into 3 categories based on the family history of cancer: group A1: families with one female case of BC diagnosed at or before 35 years of age; group A2: families with 2 or more BC cases diagnosed at any age; and group A3: families with one or more female BC cases and one or more OC cases diagnosed at any age.…”

“…In a single previous study conducted regarding this ethnic group, screening for the 4 small-scale Colombian BRCA1/2 founder mutations led to the identification of one BRCA1 mutation in 60 Afro-Colombian families affected by breast/OC. 15 To define the spectrum of mutations and to estimate mutation frequencies, we have now comprehensively analyzed the complete BRCA1/2 genes for small-scale mutations and large genomic rearrangements (LGRs) in the same sample set using next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA).…”

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia

“…We also cannot exclude that the mutation may have multiple ancestral origins in countries without a history of colonization by those countries, such as Canada or Norway, where this mutation has been also reported [ 7 , 33 ]. Furthermore, while our study in Colombia focused on communities from the central Andean region, where we have shown that they have a predominant European and Indigenous American ancestry [ 16 , 34 – 40 ], a recent study in Afro-Colombian populations from the west of the country also identified BRCA1 c.3331_3334delCAAG carriers, which may suggest additional origins in other Colombian groups [ 41 ]. A similar analysis with carriers from these populations would be necessary to confirm this hypothesis.…”