Abstract 5267: Unveiling associations between Duffy-null status and circulating chemokines among a diverse breast cancer patient cohort

Abstract Breast cancer (BC), the most diagnosed cancer and the leading cause of cancer-related mortality among women worldwide, includes triple-negative breast cancer (TNBC), its most aggressive subtype, which is disproportionately prevalent among individuals of West African ancestry. Our previous studies have demonstrated a correlation between West African ancestry-specific expression of the Duffy Antigen Receptor for Chemokines (DARC) and TNBC incidence. DARC regulates CC and CXC chemokines, maintaining homeostatic chemokine levels. However, the Duffy-null polymorphism (rs2814778), fixed in individuals of West African descent as an evolutionary defense against Plasmodium vivax malaria, results in the absence of DARC on erythrocytes. We aim to understand how this absence may influence chemokine regulation and contribute to ancestry-specific differences in the tumor microenvironment. We hypothesize that individuals with the Duffy-null genotype exhibit higher circulating chemokine levels than those with the DARC allele among BC cases. Since 2006, the International Center for the Study of Breast Cancer Subtypes (ICSBCS) has recruited patients from sites across the United States and Africa, collecting blood and tumor tissue samples. We utilized the Luminex multiplex assay to analyze plasma from the ICSBCS cohort, quantifying 50 biomarkers using the bead-based ELISA platform. Plate/batch effect normalization was done with MDimnNormn, and statistical tests were performed using JMP Pro 16. Genotyping for the Duffy-null allele (C) was conducted using TaqmanTM GTXpressTM Master Mix and specific probes on an Applied Biosystems 7500 Fast Real-Time PCR system. Our cohort included Duffy-null (CC, n = 183), Duffy-null carriers (CT, n = 40), and non-Duffy-null (TT, n = 294) individuals. Univariate analysis of chemokine levels revealed significant associations between Duffy-null status and the following biomarkers: MCP-1/CCL2 (p = 0.0116), Gro- b/CXCL2 (p = 0.0137), MIP1a/CCL3 (p = 0.0316), GCP2/CXCL6 (p = 0.0423), I-TAC/CXCL11 (p = 0.0008), BCA- 1/CXCL13 (p = 0.0252), MIP3b/CCL19 (p = 0.0023), 6Ckine/CCL21 (p = 0.0066), and MPIF1/CCL23 (p < 0.0001). These findings highlight significant associations between Duffy-null status and circulating chemokine levels, introducing novel BC biomarkers that characterize the relationship between Duffy-null status, BC, and West African ancestry. Moreover, these findings have important prognostic and therapeutic implications, particularly for addressing ancestry-specific factors in BC. Understanding these associations advances precision medicine efforts to address BC disparities affecting individuals of West African ancestry globally. Multivariate analyses to control for co-variates are ongoing to support these findings further. Citation Format: Stevens M. Patino, Kenya Bynes, Jason White, Danielle S. Doucette, Emma Guyonnet, Julie Sahler, Brian Stonaker, Avery August, Lisa Newman, Rachel Martini, Melissa Davis. Unveiling associations between Duffy-null status and circulating chemokines among a diverse breast cancer patient cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5267.