Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

Abstract

Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate-and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35.

Genetic and clinical characterization of BRCA-associated Hereditary Breast and Ovarian Cancer in Navarra (Spain)

“…In addition to these national similarities, BRCA1/2 mutations in Navarra present some unique features. [31], which may suggest a founder effect in the southwest of Navarra. This duplication has showed the highest correlation with OC in our study population:…”

Rare non-synonymous germline mutations systematically define the risk of triple negative breast cancer

“…We hypothesized that these sporadic-like cases involved germline mutations. Such sporadic-like cases often display remarkable non-Mendelian genetic features, such as polygenic traits, incomplete-and co-dominance (53,54). On the one hand, these features make it difficult to rule out familial inheritance, but on the other hand favor our hypothesis of using holistic germline information to characterize sporadic-like TNBC.…”

Association of PIN3 16-bp Duplication Polymorphism of TP53 with Breast Cancer Risk in Mali and A Meta-analysis.

“…Recent report showed that in addition to clinical, lifestyle and environmental risk factors, an individual's genetic background plays a crucial role in the development of breast cancer [3]. Several genes have been shown to be associated with an increased risk of breast cancer, such as damaged DNA repair genes (BRCA1 and BRCA2), tumor protein p53 (TP53), Checkpoint kinase 2 (CHEK2), methylenetetrahydrofolate reductase (MTHFR), broblast growth factor receptor 2 (FGFR2) and glutathione S-transferase mu 1 (GSTM1) [4]. TP53, a tumor suppressor gene, is involved not only in the development of breast cancer, but also in the development of other human cancers.…”