Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (þ) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2þ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07–1.35; P ¼ 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2þ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer.
Bibliographical noteFunding Information:
We want to thank the biobank at the Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru, for their assistance managing and storing the material for the study. We also want to thank participants from the PEGEN-BC study and the COLUMBUS Consortium. The PEGEN-BC study was supported by the National Cancer Institute (R01CA204797 to L. Fejerman) and the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). The COLUMBUS Consortium was supported by grants from School of Medicine (Dean's Fellowship in Precision Health Equity to L. Carvajal-Carmona) and support from the Office of the Provost for L. Carvajal-Carmona's Latinos United for Cancer Health Advancement, LUCHA, Initiative); GSK Oncology (Ethnic Research Initiative to L. Carvajal-Carmona and M. Echeverry); The U.S. National Institutes of Health (Cancer Center Support Grant P30CA093372 from the National Cancer Institute). L. Carvajal-Carmona, M.E. Bohorquez, and M. Echeverry are also grateful for support from Colciencias (Graduate Studentship to Jennyfer Benavides, member of COLUMBUS, from Convocatoria para la Formacion de Capital Humano de Alto Nivel para el Departamento de Tolima-COLCIENCIAS –755/2016), Universidad del Tolima (grants to M.E. Bohorquez and M. Echeverry, project 10112), and Sistema Nacional de Regalías, Gobernacion del Tolima (grants to M.E. Bohorquez and M. Echeverry, projects 520120516 and 520115). J. Torres was supported by Coordinacion Nacional de Investigacion en Salud, IMSS, Mexico, grant FIS/IMSS/PROT/PRIO/13/027 and by the Consejo Nacional de Ciencia y Tecnologia (Fronteras de la Ciencia grant 773), Mexico.
© 2020 American Association for Cancer Research.