1. JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients.
- Author
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Guerrero-Preston R, Lawson F, Rodriguez-Torres S, Noordhuis MG, Pirini F, Manuel L, Valle BL, Hadar T, Rivera B, Folawiyo O, Baez A, Marchionni L, Koch WM, Westra WH, Kim YJ, Eshleman JR, and Sidransky D
- Subjects
- Adult, Black or African American statistics & numerical data, Biomarkers, Tumor analysis, Case-Control Studies, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms ethnology, Head and Neck Neoplasms genetics, Head and Neck Neoplasms immunology, Humans, Male, Middle Aged, Prognosis, Squamous Cell Carcinoma of Head and Neck ethnology, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck immunology, Squamous Cell Carcinoma of Head and Neck mortality, Survival Rate, Tumor Suppressor Protein p53 genetics, White People statistics & numerical data, DNA Methylation, Germ-Line Mutation, Head and Neck Neoplasms mortality, Health Status Disparities, Janus Kinase 3 genetics, Lymphocytes, Tumor-Infiltrating immunology, Social Determinants of Health
- Abstract
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 < 0.05). Analyses also showed differences in the frequency of TP53 mutations ( n = 32) and tumor-infiltrating lymphocyte (TIL) counts ( n = 24), and the presence of a specific C โ A germline mutation in JAK3 , chr19:17954215 (protein P132T), in Black patients with HNSCC ( n = 73; P < 0.05), when compared with NLW ( n = 37) patients. TIL counts are associated ( P = 0.035) with long-term (>5 years), when compared with short-term survival (<2 years). We show bio-social determinants of health associated with survival in Black patients with HNSCC, which together with racial differences shown in germline mutations, somatic mutations, and TIL counts, suggests that contextual factors may significantly inform precision oncology services for diverse populations., (©2019 American Association for Cancer Research.)
- Published
- 2019
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