Page 90 - Genomic Medicine in Emerging Economies

Hereditary Breast Cancer 79

Solano et al., 2016). These studies have included patients with a family history
of breast and ovarian cancer as well as isolated patients. Among these studies
mutation prevalence is 19% (Argentina) and 21.4% (Brazil) for breast and or
ovarian cancer patients, respectively, selected by diverse criteria.
In terms of gene rearrangements described for BRCA1 and BRCA2 they seem
to be scarce in Latin American populations. Only four countries, Argentina,
Brazil, Colombia and Mexico, have reported pathogenic gene deletions and
one Alu insertion (Villarreal-Garza et al., 2015a; Ewald et al., 2016; Fernandes
et al., 2016; Solano et al., 2016) and one report from Chile presented non-
pathogenic amplifications in BRCA1 in three patients (Sanchez et al., 2011).
In Argentina three breast and two ovary cancer patients presented a deletion
in BRCA1, constituting 0.54% of total patients (Solano et al., 2016). In Brazil
two rearrangements were found in two patients (Fernandes et al., 2016), one
of those c.156_157insAlu being founder in Portugal (reviewed in Ossa and
Torres, 2016) and also described in a second Brazilian study in three patients
(Ewald et al., 2016). The two studies from Brazil give percentages of breast
cancer patients carrying a rearrangement between 0.57% and 3.4% (Ewald
et al., 2016; Fernandes et al., 2016). A study in Mexican patients with breast and
ovarian cancer, unselected for family history (Villarreal-Garza et al., 2015a) a
founder deletion in BRCA1, ex9-12del, previously described in Hispanic from
Mexican origin (Weitzel et al., 2007) was detected in 33% of mutation carriers
(6.9% of total patients).

Founder Mutations in Latin American Breast Cancer Families
In Latin America, there are a few different mutations with a demonstrated
founder effect that have been described in different populations: Mexico
(BRCA1 del exons 9–12), Brazil (BRCA1 5382insC), Colombia (BRCA1
3450delCAAG, A1708E, and BRCA2 3034del4) and US Hispanics (BRCA1
185delAG, IVS5+1G>A, S955X, and R1443X) (reviewed in Ashton-Prolla and
Vargas, 2014; Ossa and Torres, 2016). In addition to these founder mutations,
other recurrent mutations have been described in Latin American populations
in which a founder effect has still not been tested. Another relevant finding is
that founder and recurrent mutations have accounted for a high percentage of
BRCA1 and 2 mutation carriers, which have provided a great opportunity for
setting up a simple screening in breast cancer patients. So far, there have been
three examples in Latin American populations published that describe this
event. In Colombia a specific study done in 53 breast/ovarian cancer families
from Bogotá revealed the presence of three founder mutations accounting for
80% of BRCA1/2 mutation carriers (Torres et al., 2007). A study from Mexico
(Torres-Mejia et al., 2015) of 810 patients from three different cities showed
that six recurrent mutations account for 62% of total carriers. And, in Brazil
an extended study of 349 breast cancer patients described that the founder