Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

• Autores: Zavala, Valentina A., Casavilca-Zambrano, Sandro, Navarro-Vásquez, Jeannie, Castañeda, Carlos A., Valencia, Guillermo, Morante, Zaida, Calderón, Monica, Abugattas, Julio E., Gómez, Henry, Fuentes, Hugo A., Liendo-Picoaga, Ruddy, Cotrina, Jose M., Monge, Claudia, Neciosup, Silvia P., Huntsman, Scott, Hu, Donglei, Sánchez, Sixto E., Williams, Michelle A., Núñez-Marrero, Angel, Godoy, Lenin, Hechmer, Aaron, Olshen, Adam B., Dutil, Julie, Ziv, Elad, Zabaleta, Jovanny, Gelaye, Bizu, Vásquez, Jule, Gálvez-Nino, Marco, Enriquez-Vera, Daniel, Vidaurre, Tatiana, Fejerman, Laura
• Formato: artículo
• Fecha de Publicación: 2022
• Institución: Universidad Peruana de Ciencias Aplicadas
• Repositorio: UPC-Institucional
• Lenguaje: inglés
• OAI Identifier: oai:repositorioacademico.upc.edu.pe:10757/660949
• Enlace del recurso: http://hdl.handle.net/10757/660949
• Nivel de acceso: acceso abierto
• Materia: Breast Neoplasms; Female; Hispanic or Latino; Humans; Logistic Models; Peru; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; United States

Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/ Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.