Somatic mutations play an important role in cancer prognosis and can pave the way for precision medicine to overcome cancer disparities. Current models hold that solid tumors evolve from microscopic clonal cellular proliferations driven through progressive histologic stages by the acquisition of somatic alterations. The accumulation of somatic mutations is associated to varying rates of stem cell divisions, leading to replicative errors that arise in response to hereditary burden, environmental stressors, or random error. Environmental, lifestyle, and neighborhood factors track closely with the acquisition of DNA methylation alterations and may partly explain the differential accumulation of genetic alterations in cancer patients. However, the combined roles of germline and somatic mutation burden, promoter methylation, and neighborhood characteristics in cancer disparities are unknown, in large part because most of the genomic studies have been performed on genomes of European descendants. Here we show that neighborhood characteristics linked to genetic, epigenetic, and tumor-associated immune signatures differ in Black and non-Latino White (NLW) head and neck squamous cell carcinoma (HNSCC) patients. Promoter methylation in PAX genes is associated to neighborhood characteristics at the zip code level (p<0.05). We also show that the number of tumor-infiltrating lymphocytes (TILs), the frequency of TP53 mutations, and a C -> A germline mutation in JAK3, chr19:17954215 (protein P132T), differ in Black when compared to NLW HNSCC patients (p<0.05). Our results demonstrate that genetic, epigenetic, and immuno-oncology alterations differ in racially diverse HNSCC patients. TILs and JAK3 germline mutations also vary across sex and anatomic tumor site. Finally, we show that molecular alterations are linked to known neighborhood stressors at the zip code level. Together, these data suggest that paired molecular and social determinants of health at the neighborhood level can inform the delivery of precision oncology services to racial and ethnically diverse populations.
Citation Format: Rafael Guerrero-Preston, Fahcina Lawson, Laura Manuel, Blanca Valle, Tal Hadar, Bianca Rivera, Oluwasina Folawiyo, Adriana Baez Bermejo, Luigi Marchionni, Wayne Koch, William Westra, David Sidransky. Germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health differ in Black and non-Latino White head and neck cancer patients [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B43.