Page 65 - Genomic Medicine in Emerging Economies

54 CHAPTER 4: Le v er aging Int ernational Collabor ations

Native American (Carvajal-Carmona et al., 2000). This revealed the uneven
mating pattern in this region in early times, involving mainly immigrant men
with local native women, and confirmed what was historically known. Cer-
tain genetic conditions, such as metabolic disorders, bipolar disease, chorea,
schizophrenia, Tourette syndrome, and cleft palate are common in Antioquia
(Arcos-Burgos and Muenke, 2002; Camargo et al., 2012; Kremeyer et al., 2010;
Pérez-Póveda et al., 2005; Scharf et al., 2013). A founder mutation in the PSEN1
gene, known to cause a severe familial form of early-onset Alzheimer‘s disease
was also discovered in a specific region of Antioquia (Acosta-Baena et al., 2011).
The genetic background of a population is very important when studying the
incidence and mortality of certain diseases, such as breast cancer. In the United
States the incidence of breast cancer was shown to be lower in African Ameri-
cans than in white women, and mortality higher in African Americans (DeSantis
et al., 2014). Although differences in exposure to risk factors contribute to the
difference in incidence rates, and social and economic disparities can explain
the higher rates of mortality in African American women, ethnicity appears to
play an important role. In a study conducted by Fejerman et al. (2008) in Lati-
nas living in northern California, they found that a higher European ancestry
was associated with increased breast cancer risk, with an odds ratio (OR) of
1.79 for a 25% increase in European ancestry. Another study by Fejerman et al.
(2013) showed that a higher indigenous American ancestry was associated with
an increased risk of breast cancer-specific mortality (hazard ratio (HR): 1.57 per
25% increase in indigenous American ancestry). A case control study conducted
in women residing in Mexico, found that for every 25% increase in European
ancestry, there was a 20% increase in risk for breast cancer (Fejerman et al., 2010).

Regarding the study of hereditary cancers, the genetic background of a popula-
tion should also be taken into account, and sometimes cost-effective screening
tests can be developed when founder mutations are responsible for a high
proportion of cases in a given population, as is the case with Ashkenazi Jews,
where 1 in 40 people are carriers of one of three founder mutations in BRCA1/2
(Ferla et al., 2007).

In Colombia three founder mutations in the genes BRCA1 and BRCA2 (which
cause hereditary breast and ovarian cancer syndrome) were discovered in
Bogota, and were also found in subsequent studies in breast and ovarian
cancer patients in Bogota (Rodríguez et al., 2012; Torres et al., 2007, 2009).
A commercial panel test, the “Colombian profile,” was developed to study
these mutations, and until recently this was the only BRCA1/2 test covered
by the health care system in Colombia, leading to incomplete Breast cancer
gene testing and inaccurate clinical management of patients and their fami-
lies. A study in Medellin (the capital of Antioquia Province) in 2011 found
a very low frequency of these mutations in unselected breast cancer patients
(2%) (Hernández et al., 2014). Recently, our group in the IDC studied breast