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

Research output: Contribution to journalArticle

Abstract

To inform novel personalized medicine approaches Analyses also showed differences in the frequency of for race and socioeconomic disparities in head and TP53 mutations (n ¼ 32) and tumor-infiltrating lym-neck cancer, we examined germline and somatic muta-phocyte (TIL) counts (n ¼ 24), and the presence of a tions, immune signatures, and epigenetic alterations specific C ! A germline mutation in JAK3, linked to neighborhood determinants of health in Black chr19:17954215 (protein P132T), in Black patients and non-Latino White (NLW) patients with head and with HNSCC (n ¼ 73; P < 0.05), when compared with neck cancer. Cox proportional hazards revealed that NLW (n ¼ 37) patients. TIL counts are associated (P ¼ Black patients with squamous cell carcinoma of head 0.035) with long-term (>5 years), when compared with and neck (HNSCC) with PAX5 (P ¼ 0.06) and PAX1 short-term survival (<2 years). We show bio-social (P ¼ 0.017) promoter methylation had worse survival determinants of health associated with survival in than NLW patients, after controlling for education, Black patients with HNSCC, which together with racial zipcode, and tumor–node–metastasis stage (n ¼ differences shown in germline mutations, somatic 118). We also found that promoter methylation of mutations, and TIL counts, suggests that contextual PAX1 and PAX5 (n ¼ 78), was correlated with neigh-factors may significantly inform precision oncology borhood characteristics at the zip-code level (P < 0.05). services for diverse populations.

Original languageEnglish (US)
Pages (from-to)255-270
Number of pages16
JournalCancer Prevention Research
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Guerrero-Preston, R., Lawson, F., Rodriguez-Torres, S., Noordhuis, M. G., Pirini, F., Manuel, L., Valle, B. L., Hadar, T., Rivera, B., Folawiyo, O., Baez, A., Marchionni, L., Koch, W. M., Westra, W. H., Kim, Y. J., Eshleman, J. R., & Sidransky, D. (2019). JAK3 variant, immune signatures, DNA methylation, and social determinants linked to survival racial disparities in head and neck cancer patients. Cancer Prevention Research, 12(4), 255-270. https://doi.org/10.1158/1940-6207.CAPR-17-0356