Page 87 - Genomic Medicine in Emerging Economies

76 CHAPTER 5: Screening for Hereditary Cancer in Latin America

Mutational Screening of BRCA1 and BRCA2 in Latin American
Populations
The first full mutational screening on BRCA1 and BRCA2 in a cohort of heredi-
tary breast cancer patients (56 Chileans) from Latin America was published
by our group in 2006 (Gallardo et al., 2006). The selection criteria used in
this study included patients belonging to families with at least (1) three rela-
tives presenting breast cancer at any age, (2) two relatives with breast cancer
with one having been diagnosed before the age of 43, (3) one breast and one
ovarian cancer at any age, (4) one male and one female with breast cancer. We
found that 20% (11/54) of nonrelated patients presented a mutation in BRCA1
or BRCA2, with a total of seven mutations. Table 5.1 shows all reports includ-
ing patients with family history including similar selection criteria in order to
assemble genetic information on hereditary breast cancer in Latin America.
These studies revealed percentages for BRCA mutation carriers between 13.7%
and 26.3%, in Chile, Argentina, Colombia, Uruguay and Venezuela (Gallardo
et al., 2006; Jara et al., 2006; Torres et al., 2007; Delgado et al., 2011; Lara
et al., 2012; Solano et al., 2012). Among the eight studies on BRCA1 and BRCA2
mutational analysis and including familial cases of breast cancer, sample sizes
range from 16 to 97. The other three studies from Argentina, Brazil and Cuba
(Rodriguez et al., 2008; Solano et al., 2012; Carraro et al., 2013) have selected
breast cancer patients who include a criteria recommended by the National
Comprehensive Cancer Network (NCCN), such as patients with no apparent
family history who present early onset breast cancer. As seen in Table 5.2 the
number of included patients, screening techniques, and mutation rates vary
widely among these studies. Considering Argentinanian and Brazilian studies
carried on with DNA sequencing, the percentages of mutation carriers varied
between 7.9% and 13.5% (Solano et al., 2012; Carraro et al., 2013). In Chile, we
found that 11% of breast cancer patients with no apparent family history and
early-onset (<40), carry a mutation in BRCA1 or BRCA2 (Alvarez et al., 2017).
The study of 247 similar patients from Cuba (Rodriguez et al., 2008) revealed
only 0.8% of mutation carriers, which may be due to the screening technique
utilized or a real situation in this specific population. In Table 5.3 we gathered
all publications screening all exons and intron-exon boundaries of BRCA1 and
BRCA2, but including patients with mixed selection criteria either with or with-
out family history. As is shown, an additional Chilean study of 326 patients
(Gonzalez-Hormazabal et al., 2011) indicates a 7% of mutation carriers, lower
than the percentages found in previous studies in Chilean families selected
by hereditary criteria. This result reveals the importance of selection criteria
in these sort of studies. An NGS screening of 39 Mexican patients with breast
cancer showed a 10.2% of mutation carriers (Vaca-Paniagua et al., 2012). The
two most recent studies published in South America report a screening in more
than 340 patients using Next Generation Sequencing (Fernandes et al., 2016;