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

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.

Genomic ancestry and cancer among Latin Americans

“…Furthermore, Zavala et al explored the correlation between rs140068132 and other polymorphisms in the 6q25 region, examining subtype-specific breast cancer risk in Latin Americans with high Native American (NA) ancestry. Their findings revealed that rs140068132 is associated to a decreased risk of breast cancer in Peruvian adults, providing greater defense against cases with negative hormone receptor (HR−) and HER2+ [ 37 ].…”

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.…”