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

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 ¼ 0.06) and PAX1 (P ¼ 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor-node-metastasis stage (n ¼ 118). We also found that promoter methylation of PAX1 and PAX5 (n ¼ 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 ¼ 32) and tumor-infiltrating lymphocyte (TIL) counts (n ¼ 24), and the presence of a specific C ! A germline mutation in JAK3, chr19:17954215 (protein P132T), in Black patients with HNSCC (n ¼ 73; P < 0.05), when compared with NLW (n ¼ 37) patients. TIL counts are associated (P ¼ 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. A, Molecular markers, combined with external and internal environment variables, can be used as biosocial markers of head and neck cancer outcome disparities, head and neck cancer markers, and precision medicine markers for patients with head and neck cancer. B, Shows that PAX5 methylation levels inversely correlate (r ¼ À0.83) with TIL counts in patients with HNSCC. C, Shows that JAK3 expression in Black patients with HNSCC differs by anatomic location. D, Shows that Notch1 mutations and PAX1 methylation levels also differ by anatomic location and race in patients with HNSCC.

Differential mutation spectrum and immune landscape in African Americans versus Whites: A possible determinant to health disparity in head and neck cancer

“…Also, a previous analysis of 44 clinically relevant somatic mutations among high-risk HNSCC patients showed 100% of the cases to harbor TP53 mutation along with mutation in other genes (APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1) [43], In our study, AA HNSCC tumors harbored higher TP53 mutation frequency than Whites which is consistent with previous retrospective study [22], however we did not observe any difference in survival outcome. Similar elevated frequency of TP53 mutation was observed in AA HNSCC tumors with no survival difference [44].…”

Prevalence of Human Papillomavirus (HPV) Infection and the Association with Survival in Saudi Patients with Head and Neck Squamous Cell Carcinoma

“…Head and neck (H&N) cancer is the 9th most frequent malignancy worldwide, accounting for around 5% of all new cases and exhibits wide demographic variations [1,2]. The global incidence is estimated at 600,000 cases per year, with evidence indicating rising trends especially in young adults [3].…”

Head and Neck Cancers Are Not Alike When Tarred with the Same Brush: An Epigenetic Perspective from the Cancerization Field to Prognosis

“…Regarding prognosis, worse overall and/or disease-free survival in HNSCC were associated with promoter hypermethylation of KL [130], HIN1 [131], RASSF1A/RASSF2 [131], MGMT [95,119,132,133], DAPK [119], MINT31 [114], p16INK4A, and p14ARF [134]. Interestingly, PAX5 and PAX1 promoter methylation is associated with poorer overall survival in African-American patients compared to nonwhite Latinos [135].…”