Association of genetic ancestry with HER2, GRB7 AND estrogen receptor expression among Colombian women with breast cancer

Abstract

BackgroundOur previous study reported higher mRNA levels of the human epidermal growth factor receptor 2 (HER2)-amplicon genes ERBB2 and GRB7 in estrogen receptor (ER)-positive breast cancer patients with relatively high Indigenous American (IA) ancestry from Colombia. Even though the protein expression of HER2 and GRB7 is highly correlated, they may also express independently, an event that could change the patients’ prognosis. In this study, we aimed to explore the differences in ER, HER2 and GRB7 protein expression according to genetic ancestry, to further assess the clinical implications of this association.MethodsWe estimated genetic ancestry from non-tumoral breast tissue DNA and assessed tumoral protein expression of ER, HER2, and GRB7 by immunohistochemistry in a cohort of Colombian patients from different health institutions. We used binomial and multinomial logistic regression models to test the association between genetic ancestry and protein expression. Kaplan-Meier and log-rank tests were used to evaluate the effect of HER2/GRB7 co-expression on patients’ survival.ResultsOur results show that patients with higher IA ancestry have higher odds of having HER2+/GRB7- breast tumors, compared to the HER2-/GRB7- subtype, and this association seems to be stronger among ER-positive tumors (ER+/HER2+/GRB7-: OR=3.04, 95% CI, 1.47-6.37, p<0.05). However, in the multivariate model this association was attenuated (OR=1.80, 95% CI, 0.72-4.44, p=0.19). On the other hand, it was observed that having a higher European ancestry patients presented lower odds of ER+/HER2+/GRB7- breast tumors, this association remained significant in the multivariate model (OR=0.36, 95% CI, 0.13 - 0.93, p= 0.0395). The survival analysis according to HER2/GRB7 co-expression did not show statistically significant differences in the overall survival and recurrence-free survival.ConclusionsOur results suggest that Colombian patients with higher IA ancestry and a lower European fraction have higher odds of ER+/HER2+/GRB7- tumors compared to ER+/HER2-/GRB7- disease. However, this association does not seem to be associated with patients’ overall or recurrence-free survival.

Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers

“…Consistent with our findings, previous studies on the association between genetic ancestry and BC risk in Latin American populations have found differences in BC subtypes by ancestry. Rey-Vargas et al reported a higher proportion of Native American ancestry in Colombian patients with ER+ /HER2+ (45%) than in ER + /HER2− (40%) breast tumours, and Marker et al demonstrated a higher risk of HER2 + BC with increasing proportions of Native American ancestry in Colombian, Mexican and Peruvian women [ 34 , 35 ]. The novelty of the present study lay in the use of instrumental variable analysis to identify and quantify the confounding-free effect of Native American ancestry on the risk of overall BC and BC subtypes.…”

Genetic ancestry is related to potential sources of breast cancer health disparities among Colombian women

“…These samples were part of a previous study that aimed to analyze the association between genetic ancestry and ER/HER2/GRB7 status [ 22 ], and for this study, sample size was estimated based on the median fraction of IA ancestry for the Colombian population according to previous published data [ 23 ], using an absolute error of 5%. This research was approved by the Colombian NCI ethics committee and defined as risk-free, therefore, according to the Colombian laws, it was considered that no informed consent was required.…”

Oncologic anthropology: Global variations in breast cancer risk, biology, and outcome

“…Oncologic anthropology is also relevant in studying the breast cancer burden of Latina/Hispanic women internationally 27–40 . Ancestry‐associated variants have been identified that predict risk from specific breast cancer phenotypes among Latina women in the United States, in Central America, and in South America.…”

“…Oncologic anthropology is also relevant in studying the breast cancer burden of Latina/Hispanic women internationally. [27][28][29][30][31][32][33][34][35][36][37][38][39][40] Ancestry-associated variants have been identified that predict risk from specific breast cancer phenotypes among Latina women in the United States, in Central America, and in South America. These studies have also found that among admixed Latina women, the extent of European ancestry increases the risk of breast cancer, whereas extent of Indigenous American ancestry decreases the risk of breast cancer.…”