New research from Peru shows a link between a greater incidence of HER2-positive breast cancer in women with Indigenous American (IA) ancestry, suggesting the presence of a population-specific genetic variant. Researchers with the Peruvian Genetics and Genomics of Breast Cancer study (PEGEN-BC) reported on genome-wide data from 1,312 patients who had received a diagnosis of invasive breast cancer from 2010 and were between the ages of 21 and 79 years. HER2-positive breast cancers accounted for 30% of cases. Their research was published in Cancer Research.
Peru is one of the countries in Latin America with extremely high proportions of IA ancestry. On average, participants in the study had approximately 76 percent IA ancestry, with 9.8 percent of patients having greater than 95% IA ancestry.
Analyses revealed statistically significant differences in the distribution of different breast cancer subtypes among women with different proportions of IA ancestry. The odds of having a HER2-positive tumor were 1.19 times higher for every 10% increase in IA ancestry. Conversely, the odds of developing HER2-positive disease decreased with increasing European ancestry. The observed associations were independent of the participant’s age at diagnosis, level of African ancestry, height, tumor stage at diagnosis, and region of residence.
To confirm their findings, the researchers were replicated the study with 616 individual patient samples from Mexico and Colombia. In these populations, the odds of having a HER2-positive tumor was approximately 1.28 times greater for every 10% increase in IA ancestry.
The research team previously found that a higher degree of IA genetic ancestry is associated with a lower incidence of breast cancer overall. But, the influence of IA ancestry on different breast cancer subtypes remained unclear. A prior study that examined a small cohort of Colombian patients with breast cancer suggested that a higher proportion of IA ancestry was associated with increased expression of the ERBB2 gene, which encodes HER2. Together, these findings prompted the researchers to study whether IA ancestry may be associated with risk of HER2-positive breast cancer.
“Multiple studies have reported a higher incidence of HER2 tumors in women of Latin American origin,” the authors write. “The results of the current analysis in patients with breast cancer from Peru—and including independent replication in patients from Mexico and Colombia—strongly suggest there could be population-specific genetic variant(s) increasing the risk of HER2 tumors among women with IA ancestry.”
However, the authors acknowledge that other factors could be contributing to this link with HER2-positive tumors that were not included in this study, including environmental and lifestyle influences. Looking ahead, they plan on conducting further studies to confirm the genetic basis of this association and discover specific regions or variants within the IA genome.