Abstract Background: Black women experience poor survival from epithelial ovarian cancer (EOC), for all stages at diagnosis and EOC histotypes. We present findings of the contribution of African ancestry and an ancestry-related genotype in the Atypical Chemokine Receptor 1 (ACKR1) gene to EOC survival among a cohort of Black/African American women. We also report associations with tumor molecular features that may explain the potential underlying biology related to the Duffy-null ACKR1 genotypes. Methods: The relationship between global African ancestry and the rs2814778 SNP in the promotor region of the ACKR1 gene and survival was determined in a cohort of 408 Black women with EOC (275 with high grade serous ovarian cancer (HGSC)) who participated in the population-based African American Cancer Epidemiology Study (AACES) using a Bayesian modeling approach adjusting for stage, age at diagnosis, the Yost index for socioeconomic status, education, and ovarian cancer family history. Proportion of global African ancestry and the ACKR1 genotype (Duffy-null (CC) vs. TC/ TT) were determined from germline DNA. Tumor molecular features including gene expression using RNAseq, tumor immunity (i.e., T-cell abundance) measured using multiplex immunofluorescence (mIF), and homologous recombination deficiency (HRD) derived from whole exome sequencing data were generated from HGSC tumors. Results: The Duffy-null genotype was present in 70.6% EOC cases overall, and 72.0% of HGSC. The prevalence was higher among individuals with high African ancestry (African ancestry 83.6%) than those with lower African ancestry (83.2% and 58.3%, respectively). The Duffy-null genotype was associated with improved survival among EOC cases (adjusted Hazard Ratio (HR)=0.59, 95% credible intervals (CI): 0.35-0.96). The corresponding HR for HGSC was 0.61 (95% CI: 0.34-1.12). However, global African ancestry—as indicated by a 1% increase in percent African ancestry on the logit scale—was suggestively associated with worse survival, especially for HGSC, with an HR of 1.31 (95% CI: 0.89-1.90). Additionally, we examined the relationship between the CC vs. TC/ TT genotypes and tumor molecular features in HGSC. The Duffy-null genotype was associated with lower ACKR1 expression, lower cytotoxic T cell abundance, and higher HRD in HGSC. Among EOC subjects, mIF-derived myeloid cells (CD11b+) showed lower abundance in those with high African ancestry, which is consistent with worse survival. Conclusion: The Duffy-null genotype is associated with ∼40% decreased EOC mortality in Black women. Lower T-cell infiltrates may reflect lower immune surveillance and may coincide with higher HRD in HGSC among Duffy-null individuals. The HRD finding, in particular, may explain the improved prognosis observed with the Duffy-null genotype, as our group has previously shown that HRD status was associated with better survival in Black women with HGSC. Citation Format: Joellen M. Schildkraut, Jeffrey R. Marks, Xintian Song, Yao Xin, Anthony J. Alberg, Lauren C. Peres, Katherine Anne Lawson-Michod, Lindsay Jane Collin, Jennifer A. Doherty, Andrew B. Lawson, on behalf of the African American Cancer Epidemiology Study. African ancestry, Duffy-null genotype, and epithelial ovarian cancer in a cohort of Black women abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2340.
Schildkraut et al. (2026) studied this question.