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.
Original language | English |
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Pages (from-to) | 1602-1609 |
Number of pages | 8 |
Journal | Cancer Epidemiology Biomarkers and Prevention |
Volume | 31 |
Issue number | 8 August |
DOIs | |
State | Published - Aug 2022 |
Bibliographical note
Funding Information:The PEGEN-BC study was supported by the National Cancer Institute of the National Institutes of Health under award number (R01CA204797; to L. Fejerman). The PrOMIS study was supported by the National Institute of Child Health and Human Development of the National Institutes of Health under award number (R01-HD-059835; to B. Gelaye). We want to thank the biobank at the Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru, for their assistance managing and storing the material for the study. We also want to thank participants from the PEGEN-BC and PrOMIS studies. Research supported by the 2021 AACR-Genentech Cancer Disparities Research Fellowship, Grant Number 21-40-18-ZAVA (to V.A. Zavala).
Funding Information:
The PEGEN-BC study was supported by the National Cancer Institute of the National Institutes of Health under award number (R01CA204797; to L. Fejerman). The PrOMIS study was supported by the National Institute of Child Health and Human Development of the National Institutes of Health under award number (R01-HD-059835; to B. Gelaye). 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 and PrOMIS studies. Research supported by the 2021 AACR-Genentech Cancer Disparities Research Fellowship, Grant Number 21-40-18-ZAVA (to V.A. Zavala).
Publisher Copyright:
© 2022 The Authors.