Page 101 - Genomic Medicine in Emerging Economies

90 CHAPTER 5: Screening for Hereditary Cancer in Latin America

(7,8-dihydroxy-8-oxoguanine, also named 8-oxo-G) pairs adenine instead
of cytosine during DNA replication leading into a genetic transvertion of
guanine:citosine for timine:adenine (G:C > T:A). Normally, MUTYH excises
these adenines mispaired with oxidized guanine (Oka and Nakabeppu, 2011).
Hence, the absence of MUTYH function leads to an increase somatic muta-
tions, in target genes as APC and in addition an escape from programed cell
death permitting tumor development (Al-Tassan et al., 2002).
To date, 308 different MUTYH genetic alterations have been reported in the
LOVD (http://www.lovd.nl/MUTYH). Most correspond to nucleotide substitu-
tions (97.6%) and in less proportion genomic rearrangements (2.3%). Two
genetic variants have been frequently reported in Caucasian populations:
p.Y165C (c.494A>G) in exon 7 and p.G382D (c.1145G>A) in exon 13, 535
and 509 times, respectively. A meta-analysis for these two variants determined
that MUTYH homozygous carriers demonstrated a 28 fold increased risk of
colorectal cancer (95% CI: 6.95–115), and monoallelic carriers have a mar-
ginal effect with a OR = 1,34 (95% CI: 1.00–1.80) (Theodoratou et al., 2010).

Mutational Screening of MUTYH in Latin America
In total, only four countries in Latin America have published studies on the
mutational screening of MUTYH: Argentina, Brazil, Puerto Rico, and Chile
(De Rosa et al., 2004; Álvarez et al., 2012; Cruz-Correa et al., 2013; Torrezan
et al., 2013). The selection criteria included patients with FAP patients negative
for APC mutations or attenuated FAP. As shown in Table 5.6, Caucasian muta-
tions (Y165C and G382D) are highly frequent in Puerto Rican (10/13) and
Brazilian (4/6) FAP patients (118,122). On the contrary, in Argentina no muta-
tions have been identified (De Rosa et al., 2004), and in Chile the only muta-
tion detected was c.340c>T/p.Y114H in homozygocity (unpublished results)
(Álvarez et al., 2012).

CONCLUSION

Mutational screening in cancer genes, more specifically in breast and colorectal
cancer, has been extensively studied in Latin American populations in the last
10 years. Valuable information has been gathered on the genetics of these two
types of cancer, which is compiled and discussed in this chapter. Even though
cancer patients from some countries have not yet been tested, the informa-
tion gathered to date from studies in populations across Latin America gives
relevant genetic data. We have reliable estimates on the percentages of muta-
tions carriers in genes of high risk for these two types of hereditary cancer and
enough expertise in gene screening in several Latin American countries. On the
basis of these genetic analyses the clinical management of patients has been
improved and will surely derive result in better life expectancy for patients,
now and in the future.