JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients

To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with PAX5 ( P = 0.06) and PAX1 ( P = 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor–node–metastasis stage ( n = 118). We also found that promoter methylation of PAX1 and P AX5 ( n = 78), was correlated with neighborhood characteristics at the zip-code level ( P TP53 mutations ( n = 32) and tumor-infiltrating lymphocyte (TIL) counts ( n = 24), and the presence of a specific C → A germline mutation in JAK3 , chr19:17954215 (protein P132T), in Black patients with HNSCC ( n = 73; P n = 37) patients. TIL counts are associated ( P = 0.035) with long-term (>5 years), when compared with short-term survival (