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

Area of Science:

• Genetics
• Oncology
• Population Health

Background:

• Breast cancer incidence varies among ethnic groups in the US.
• A known Indigenous American germline variant, rs140068132, near the estrogen receptor 1 gene, shows protective effects.
• This study focuses on Hispanic/Latina women with high Indigenous American ancestry.

Purpose of the Study:

• To investigate the association between the rs140068132 variant and other polymorphisms in the 6q25 region.
• To determine the impact of these variants on subtype-specific breast cancer risk in Hispanic/Latina women.

Main Methods:

• Genotyping of 5,094 Peruvian women (1,755 with breast cancer, 3,337 without).
• Logistic regression and conditional analyses to test genotype-risk associations.
• Inclusion of other risk-associated polymorphisms in the 6q25 region.

Main Results:

• Replication of the association between rs140068132 and overall breast cancer risk reduction (OR, 0.53).
• rs140068132 showed lower odds for hormone receptor-negative (HR-) versus HR+ disease (OR, 0.77).
• Further heterogeneity observed with HER2-positive subtypes, with reduced odds for HR+HER2+ and HR-HER2+ diseases.

Conclusions:

• The rs140068132 polymorphism significantly decreases breast cancer risk in Peruvians.
• The variant offers protection against HR- and HER2+ breast cancer subtypes.
• These findings highlight the importance of genetic diversity in research and could guide functional studies.