The Duffy-Null genotype and epithelial ovarian cancer survival in a cohort of Black women

Abstract

Objective. Black women experience poor survival from epithelial ovarian cancer (EOC) for all stages at diagnosis and histotypes. The contribution of an ancestry-related genotype in the Atypical Chemokine Receptor 1 (ACKR1) gene to mortality after an EOC diagnosis in Black women has not been previously reported. Methods. The relationship between the Duffy-null genotype (CC) in the ACKR1 gene and overall post-enrollment mortality in 408 Black women with EOC, including 275 with high-grade serous ovarian cancer (HGSC) was evaluated using Bayesian modeling approach to estimate hazard ratios (HR) and 95% credible intervals (CI) adjusting for stage, age at diagnosis, socioeconomic factors, and ovarian cancer family history. Tumor immune and genetic features were generated from sequencing assays on subsets of the HGSC cases. Results. The CC genotype was associated with reduced all-cause mortality among EOC cases (adjusted HR=0.60, 95% CI: 0.36–0.99). Among HGSC, the CC genotype was associated with higher African origin, lower ACKR1 expression (p=0.049), lower cytotoxic T cell abundance (p=0.062), and a higher frequency of homologous recombination deficient (HRD) tumors (p=0.051). Conclusions. In this study, the Duffy-null CC genotype was associated with 40% lower EOC all-cause mortality in Black women. These are hypothesis-generating findings that require replication and further inquiry into mechanisms.