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

Rafael Guerrero-Preston*, Fahcina Lawson, Sebastian Rodriguez-Torres, Maartje G. Noordhuis, Francesca Pirini, Laura Manuel, Blanca L. Valle, Tal Hadar, Bianca Rivera, Oluwasina Folawiyo, Adriana Baez, Luigi Marchionni, Wayne M. Koch, William H. Westra, Young J. Kim, James R. Eshleman, David Sidransky

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    4 Citations (Scopus)

    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 PAX5 (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 -> 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 (

    Original languageEnglish
    Pages (from-to)255-270
    Number of pages16
    JournalCancer Prevention Research
    Volume12
    Issue number4
    DOIs
    Publication statusPublished - Apr-2019

    Keywords

    • SQUAMOUS-CELL CARCINOMA
    • HUMAN-PAPILLOMAVIRUS HPV
    • RACIAL/ETHNIC DISPARITIES
    • AFRICAN-AMERICAN
    • EPIGENETIC INACTIVATION
    • SOMATIC MUTATIONS
    • GENE-EXPRESSION
    • BREAST-CANCER
    • POSITIVE HEAD
    • LUNG-CANCER

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