Association Between Ancestry-specific 6q25 Variants And Breast Cancer Subtypes In Peruvian Women
Document Type
Article
Publication Date
8-1-2022
Publication Title
Cancer Epidemiology Biomarkers and Prevention
Abstract
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.
First Page
1602
Last Page
1609
PubMed ID
35654312
Volume
31
Issue
8 August
Recommended Citation
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; and Gálvez-Nino, Marco, "Association Between Ancestry-specific 6q25 Variants And Breast Cancer Subtypes In Peruvian Women" (2022). School of Medicine Faculty Publications. 611.
https://digitalscholar.lsuhsc.edu/som_facpubs/611
10.1158/1055-9965.EPI-22-0069