Abstract B118: Neighborhood deprivation and the breast tumor transcriptome: Distinct associations by race and estrogen receptor status

Abstract

Non-Hispanic Black (NHB) women and women in deprived neighborhoods bear a disproportionate burden of aggressive breast cancer, but pathways linking neighborhood environment to tumor biology remain poorly defined. We characterized associations between neighborhood deprivation and the breast tumor transcriptome, overall and by race and estrogen receptor (ER) status. We included 156 women with a first primary breast cancer at Emory University Hospitals. Patient addresses were geocoded, and the neighborhood deprivation index was derived at the census block group level, categorized into tertiles and linked to patient data. We estimated differential expression for the second and third tertiles versus the first. Tumor gene expression was measured by RNA sequencing (50,058 genes; those with nonzero counts in <10% of samples excluded). Expression was modeled with DESeq2, adjusting for age, race, and ER status, with the stratifying variable omitted from stratified models; log2 fold changes (Log2FC) were shrunk using apeglm, and false discovery rate (FDR)-adjusted p<0.05 with |Log2FC|>1 considered significant. Pathway enrichment (Gene Ontology [GO], KEGG) used clusterProfiler (FDR<0.05), overall and stratified by race (NHB vs non-Hispanic White [NHW]) and ER status. The second deprivation tertile was associated with upregulated CYP2A7 (Log2FC=3.45, FDR=5.8x10-10) and the third with MUC19 (Log2FC=3.85, FDR=1.2x10-7); both persisted after smoking adjustment. Enriched pathways differed across race strata. Among NHB women, deprivation was associated with upregulated retinol metabolism (normalized enrichment score [NES]=2.30), chemical carcinogenesis-DNA adducts (NES=2.26), and cytochrome P450-mediated xenobiotic metabolism (NES=2.22), driven predominantly by CYP2A6/CYP2A7. Among NHW women, deprivation was associated with broad downregulation of genome maintenance programs, including DNA recombination (NES=-2.03), double-strand break repair (NES=-2.03), and DNA replication (NES=-1.96), with all 28 enriched GO terms negative. Parallel downregulation of repair and chromosome segregation occurred in ER-negative tumors; because this signal was strongest in NHW women, it likely reflects a pattern independent of the racial distribution of ER-negative disease. After smoking adjustment, NHB metabolism pathways persisted, whereas NHW findings did not. Tumor expression programs associated with deprivation differed between NHB and NHW women: carcinogen-metabolism upregulation concentrated in a small set of cytochrome P450 genes among NHB women, compared with broad suppression of DNA repair and replication among NHW women. These distinct programs suggest different biological responses to deprivation by race and may help explain attenuated deprivation-outcome associations previously observed in NHB women. Findings require confirmation in larger studies with power to formally evaluate interaction by race, alongside epigenome-wide integration.Generative AI was used to assist in drafting and editing the text of this abstract. Jasmine Miller-Kleinhenz, Yinxian Chen, Lauren E. Barber, Lauren E. McCullough, Lindsay J. Collin. Neighborhood deprivation and the breast tumor transcriptome: Distinct associations by race and estrogen receptor status [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr B118.