ASA Main Site  |  Past & Future Meetings
American Surgical Association

Back to 2022 Abstracts


Dissecting the Interplay Between Genetic Ancestry and Neighborhood Socioeconomic Status on Triple Negative Breast Cancer
Daniel Rodriguez1, Sina Yadegarynia1, William Harbour2, Erin Kobetz3, Nipun Merchant1, Neha Goel1
1Surgery, University of Miami, Miami, Florida, United States, 2Ophthalmology, University of Miami, Miami, Florida, United States, 3Medicine and Public Health Sciences, University of Miami, Miami, Florida, United States

Objectives: Higher rates of aggressive breast cancer subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in Black women [Hispanic (HB) and non-Hispanic (NHB)] and women from low neighborhood socioeconomic status (nSES). However, the complex relationship between race/ethnicity, nSES, and BC subtype etiology and outcomes remains unknown. To bridge this critical knowledge gap, we investigated the impact of genetic ancestry and nSES on incidence of BC subtype. We further analyzed the impact of genetic ancestry on the BC genome to identify ancestry specific regions associated with TNBC and their influence on gene expression.
Methods: Genomic analysis was performed on the peripheral blood from a cohort of 309 stage I-IV non-Hispanic White (NHW), Hispanic White (HW), HB and NHB women with BC. Patient (age, nSES) and tumor characteristics (stage, subtype) were collected. Global and local ancestral estimates using >100,000 single nucleotide polymorphisms (SNPs), were calculated against reference samples from European (EU), West African (WA), Native American (NA), and East Asian (EA) ancestral populations. Multinomial logistic regression was performed to determine predictors of TNBC compared to ER+/HER2-, ER+/HER2+, and ER-/HER2 disease.
Results: There were 192 self-reported HW, 11 HB, 46 NHW, 47 NHB, and 12 unknown (declined to report) patients. Multinomial logistic regression revealed a significant association between increasing WA ancestry and TNBC (HR 1.07,95%CI 0.003-0.12, p=0.039) as well as lower nSES and TNBC (HR 2.6, 95%CI 0.16-1.75, p=0.018). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (HR 1.06, 95%CI-0.008-0.122, p=0.089). Local ancestry analysis however still revealed nSES-independent enriched WA ancestral SNPs centered at chr2:42004914 (p=1.19x10-5) and chr5:12714599 (p=1.20x10-5) in patients with TNBC. Specifically, SNPs surrounding chr2:42004914 are expression quantitative trait loci (eQTL) impacting the expression of COX7AR, a stress-inducible mitochondrial COX subunit associated with aggressive BC (Fig 1).
Conclusions: In this integrative approach studying genetic ancestry and nSES on BC subtype, we found that increasing WA ancestry is associated with higher rates of TNBC. However, on multinomial regression adjusting for WA ancestry, low nSES had a greater influence on aggressive BC subtype and women from these regions were more than twice as likely to have TNBC regardless of ancestry. We also identified specific chromosomal segments associated with WA ancestry and TNBC, independent of nSES. We are further exploring ancestry-associated genomic regions of interest and attempting to identify gene-environment interactions that might be driving TNBC in disadvantaged neighborhoods (independent of WA ancestry) to improve patient stratification, prognostication, and identify novel therapies for women with TNBC.


Figure 1: Multitrack Manhattan plot of local European, West African, and Native American ancestries by Subtype for TNBC. X-axis, chromosome position; Y-axis, -log10(p value) for the association between TNBC and local ancestry at each variant, correcting for global ancestries, age, stage, and nSES. Each dot represents a SNP tested in the multinomial regression. Horizontal dashed lines represent enrichment with SNPs reaching this threshold are marked in gold (e.g., COX7LR chr2:42004914).


Back to 2022 Abstracts