ArticleGenome medicine2026
African ancestry and risk variants associated with triple-negative breast cancer susceptibility in African American women.
Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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24 authors.
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Abstract
backgroundCompared to European American women, African American women are more likely to be diagnosed with triple-negative breast cancer (TNBC). This difference may be partially due to genetic factors. This study aims to investigate associations of African ancestry and risk variants with TNBC among African American women.
methodsWe used data from 2,335 TNBC cases, 8,159 estrogen receptor (ER)-positive cases, and 9,814 controls included in the African-ancestry Breast Cancer Genetics (AABCG) Consortium. The proportion of African ancestry (%AFR) and local ancestry were estimated using samples from the 1000 Genomes Project as reference. Logistic regressions were performed for case-control (TNBC vs. control) and case-case (TNBC vs. ER-positive) comparisons, adjusted for age, study, genotype principal components 2-5, body mass index, and reproductive factors. Local ancestry-aware association analyses were conducted in 12 TNBC risk loci to identify ancestry-specific risk variants.
resultsIn case-control analyses, no statistically significant association was found between %AFR and TNBC risk after adjustment for potential confounders. However, TNBC cases had a significantly higher mean % AFR (mean = 0.811, standard deviation, SD = 0.104) compared to ER-positive cases (mean = 0.798, SD = 0.110, P < 0.001). Females with %AFR of ≥ 95% had 1.62 times higher odds (95% confidence interval, CI: 1.16-2.25) of having TNBC rather than ER-positive breast cancer, compared to those with %AFR of 55.0-64.9%. Local ancestry-aware association analyses identified seven subtype-informative variants in or near MDM4, RP11-19E11.1, TERT, MRPL36, TCF7L2, C11orf65, and ANKLE1. All of them were significantly associated with TNBC as compared with ER-positive cases, and six of them were also associated with TNBC risk in case-control analyses. Large allelic odds ratios of 1.25 or higher were found in association with TNBC risk or subtype classification. The risk allele frequency for five of them is substantially higher in haplotypes of African ancestry than those of European ancestry.
conclusionsThese findings support a significant role of African-ancestry specific genetic factors in determining breast cancer subtypes and highlight the need for future research to uncover possible pathways driving TNBC susceptibility.
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