Racial disparities in mycosis fungoides - from self-reported race to genetic ancestry analysis

Abstract Introduction: Racial disparities in mycosis fungoides (MF) and Sezary syndrome (SS) are well-documented, with self-identified Black patients being diagnosed younger, with more advanced disease, and worse survival. (Su C et al. J Am Acad Dermatol. 2017; Wilson LD et al. Clin Lymphoma Myeloma Leuk. 2012). Our previous work showed that these disparities persist after adjusting for socioeconomic factors (Gandham AR et al. Clin Lymphoma Myeloma Leuk. 2024) suggesting genetic ancestry may contribute. We compared clinical characteristics and outcome of MF/SS patients stratified by self-reported race versus genetic ancestry. Methods: Patients with confirmed MF/SS were consented for genetic profiling via Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). Genetic ancestry was inferred using ADMIXTURE and single nucleotide polymorphisms (SNPs) captured by MSK-IMPACT (Arora K et al. Cancer discovery. 2022). Patients with ancestral fraction of >0.8 for any single population were assigned that population label; otherwise, they were considered admixed. Results: Genetic ancestry analysis of 161 MF/SS patients (104 self-reported White race, 30 Black, 7 Asian, 20 Other/Unknown) identified 74 as European (EUR), 21 Ashkenazi Jewish (ASJ), 23 African (AFR), 5 East/South Asian, 1 Native American and 37 as admixed. AFR patients were diagnosed 10 years younger than EUR/ASJ (p=0.01) and were less likely to present with stage IA disease compared to EUR/ASJ patients (0% vs 23.2%, p=0.01). Trends towards higher female dominance (52% vs. 35%, p=0.1), higher disease-related mortality (22% vs 12%, p=0.2) and worse progression-free survival (PFS, p=0.11) were observed in AFR patients. ASJ patients showed a trend toward improved PFS compared to EUR patients (p=0.08). Conclusions: Our novel ancestry-based stratification of MF/SS patients confirms disparities seen in self-reported race groups, supporting the need to further investigate specific genetic and non-genetic contributors to disparities in MF/SS patients.