Page 83 - Genomic Medicine in Emerging Economies

72 CHAPTER 5: Screening for Hereditary Cancer in Latin America

or other equivalent, and Protein Truncation Test (PTT), supported by Sanger
sequencing in specific fragments. Full sequencing by Sanger has been widely
used in mutational screening since about 2008 to 2010, and in the last 3 to
4 years next-generation sequencing has become more commonly used. In this
regard, the countries having installed this latter technology are Mexico, Brazil,
Chile, Argentina and Uruguay. One of the main problems in using our own
NGS facilities is that the higher prices of the reagents, shipping and taxes, in
addition to a low number of analyzed samples make NGS more expensive than
in developed countries.
In Latin America, research in hereditary cancer has been mainly focused on
breast and colon cancer because of the widely available information relating
to the genetics of these two types of cancer and the high occurrence of these
malignancies as well.

HEREDITARY BREAST CANCER

Clinical and Genetic Features
Since the identification of the two genes BRCA1 and BRCA2 (Hall et al., 1990;
Miki et al., 1994; Wooster et al., 1995) mutations of which confer a high risk of
breast cancer many populations have been screened by selecting women hav-
ing a strong family history of breast and ovarian cancer. In the first few years
(1995–2000), the criteria for selecting patients for BRCA1 and BRCA2 screen-
ing included only first- degree relatives affected by breast or ovarian cancer.
Over the years, several studies in which selection criteria of the patients’ were
expanded to second degree relatives and isolated patients diagnosed under
40 years, among others, revealed that additional breast cancer patients must
be screened for mutations in BRCA1 and BRCA2. For this reason, different
studies published from Latin American countries, since the identification of
BRCA1 and BRCA2, show different selection criteria of breast cancer patients
(Table 5.1). In addition to differences in selection criteria a variety of experi-
mental approaches have been utilized, in relation to screening techniques and
the analysis of selected exons or total exons of BRCA1 and BRCA2 (Table 5.1).
In this chapter, we will present studies carried on mainly within Latin America
in which a full screening of BRCA1 and BRCA2 has been accomplished, and we
will discuss on the different screening technologies used, as well as the criteria
for breast cancer patients’. Even if penetrance of mutations at 70 years old has
been estimated between 52% and 47% for BRCA1 and BRCA2, respectively, for
other populations (Chen and Parmigiani, 2007; Milne et al., 2008), no studies
have been performed in this regard in Latin American high-risk families. This
is a very important issue since genetic and nongenetic features may influence
penetrance.