Page 86 - Genomic Medicine in Emerging Economies

Hereditary Breast Cancer 75

Amerindian or European Ancestry and Breast
Cancer Incidence
It has been demonstrated that breast cancer prevalence is variable depending
on the ancestry composition of populations. For example, Asian countries have
the lowest incidence rates of breast cancer (20–30/100,000 women), and Cauca-
sian populations such as Europe (80–100/100,000 women) and North America
(120/100,000 women) have the highest (GLOBOCAN 2012). In relation to Latin
American populations the incidence of breast cancer ranges from 24/100,000 to
71/100,000, with Argentina, Uruguay and Brazil having the highest incidences.
It is interesting that the Hispanic population living in the United States has a
higher breast cancer incidence (91.9/100,000) than those living in their coun-
tries of origin, but lower that Non-Hispanic whites (128.1/100,000). According
to GLOBOCAN, the SEER Cancer Statistics Review (Howlader et al., 2016) states
that US women of European ancestry have a greater risk of breast cancer than US
women with indigenous ancestry. These differences may be caused by genetic
and/or nongenetic factors to which these populations are exposed. In this con-
text, it has been demonstrated by Fejerman et al. (2008) that European ancestry
constitutes a relevant genetic risk factor to breast cancer, among US Hispanics,
with an OR = 1.79 for every 25% increase in European ancestry. In addition, the
ancestry analysis for Mexican women residing in Mexico showed that for every
25% increase in European ancestry there was a 20% increase in risk (Fejerman
et al., 2010). In this context Uruguay, which has the highest incidence of breast
cancer (71/100,000) in South America, has an average European ancestry of
76.6% (Bonilla et al., 2015). Bonilla et al. (2015) found a positive association of
breast cancer in Uruguayan women with European ancestry (mitochondrial hap-
lotype H), and an inverse association with Native American ancestry. An interest-
ing finding revealed by a GWAS performed in Latin American women, showed a
SNP in the ESR1 (estrogen receptor α gene) rs140068132, conferring protection
against breast cancer. This SNP is present in 5%–15% of Latin American women
depending on the Amerindian ancestry component. Carriers of this SNP present
an OR = 0.6 (95% CI 0.53–0.67; p < 9 × 10 −18 ) (Fejerman et al., 2014).

Our group analyzed Amerindian mitochondrial DNA haplogroups in a sample
of 77 Chilean women with breast cancer and found a significant lower per-
centage of the matrilineal Amerindian component (69%) compared with the
admixed general population in Chile (84%) (Rocco et al., 2002; Gallardo
et al., 2006). Even when mitochondrial DNA markers represent only a matri-
lineal ancestry, this result is consistent with those mentioned earlier. In rela-
tion to AIMs no breast cancer studies have been published as such, but this is
in need of further study. In Chile, the genetic structure of our population has
been studied by “Chilegenómico” and others (http://www.chilegenomico.cl)
(Ruiz-Linares et al., 2014; Eyheramendy et al., 2015). These results revealed
that the Chilean population is on average 51% European, 5% African, and
44% Amerindian, with no relevant variations in percentages along Chile.