Page 92 - Genomic Medicine in Emerging Economies

Lynch Syndrome 81

mutations recurrent in Hispanic breast cancer patients from the United
States, Mexico, and Colombia, as other mutations taken from publications
(Weitzel et al., 2013) (patent application US 20130183667A1). This panel was
applied to 280 breast cancer patients at a hospital in Medellin (Colombia)
unselected for family history, finding only 1.2% of mutation carriers (Hernán-
dez et al., 2014). A similar study was performed in 266 patients from a pub-
lic Hospital in Lima, finding 5% of mutation carriers (Abugattas et al., 2015),
among which the Ashkenazi Jewish mutation 185_186delAG was present in 7
of 13 patients with mutations. The main issue with this panel is, as has been
noticed already (Ashton-Prolla and Vargas, 2014), that recurrent mutations
among Latin American countries are different, so a panel trying to gather all
these mutations will not be successful.

Ashkenazi Jewish founder mutations (185delAG, 5382insC in BRCA1 and
6174delT in BRCA2) have been observed in several Latin American countries,
although in Brazil and Argentina they are highly recurrent. Mutation 5382insC,
which is not exclusively Ashkenazi Jewish (Hamel et al., 2011), was described
in 2007 in Brazilian patients. Posterior screening of a wider Brazilian popula-
tion, found 18% and 24% of patients with the 5382insC mutation (Carraro
et al., 2013; Fernandes et al., 2016). In Argentina the three mutations were
represented, being 185delAG being the most recurrent with 13.4%, 6174delT
with 11.7% and 5382insC with 7.8% (Solano et al., 2016). Together the three
mutations account for 33% of all mutations carriers in Argentina (Solano
et al., 2016). In Chile, considering all studies, only 5.3% of patients carry one
of the three Jewish Founder mutations. In Costa Rica, only mutation 6174delT
has been identified but in one patient (Gutiérrez Espeleta et al., 2012). Muta-
tion 185delAG has been found in Mexico and Peru through HISPANEL analy-
sis with frequencies 2.5%–6.8% in Mexico (Villarreal-Garza et al., 2015a,b)
and 53.8% in Peru (Abugattas et al., 2015).

LYNCH SYNDROME
Clinical and Genetic Features
In 1984, the term Lynch syndrome was proposed to describe families with
colorectal and gynecological cancer with a lack of polyposis phenotype, and
this term has been commonly used since then (Boland and Troncale, 1984).
This Syndrome is the most common inheritable type of colorectal cancer,
accounting for 2%–4% of the cases, and has an estimated prevalence in the
general population of 1 in 440 (Hampel et al., 2005; Hampel et al., 2006;
Rubenstein et al., 2015). Although the term hereditary nonpolyposis colorec-
tal cancer (HNPCC) is often used interchangeably with Lynch syndrome, it is
important to remember that HNPCC is a clinical diagnosis for patients and/or
families that meet Amsterdam I or II criteria, whereas the diagnosis of Lynch