ABSTRACT
Non-Hispanic Black/African American (AA) individuals develop non-small cell lung cancer (NSCLC) 5 years
earlier than their non-Hispanic White (NHW) counterparts. AAs also have a higher lung cancer incidence and
mortality rates. The role of structural racism in the development and maintenance of these disparities has been
understudied. Our long-term goal is to achieve health equity within NSCLC through investigations that benefit
the AA community. The objective of this proposal is to determine the impact of racism-related socio-
environmental factors, including air pollution and residential segregation on the mutagenic process in NSCLC
tumors of AA patients. The central hypothesis is that measurable structural racism stressors induce changes in
mutational processes that negatively impact disease progression in AA patients with early-stage NSCLC. Our
study rationale is that genomic data from AA NSCLC specimens is lacking, which hinders understanding of the
disease etiology and progression in this vulnerable population. For example, only 82 of 1,053 patients in The
Cancer Genome Atlas reported identifying as African American. In addition, it is imperative to determine the
extent to which racism-related socio-environmental factors affect the distribution of mutational signatures in
NSCLC tumors in AA patients in order to identify specific pathways linking structural racism stressors to worse
outcomes and yield targets for intervention and biomarkers for risk stratification. We propose to survey 200 AA
patients with stage I–II NSCLC identified from California and Georgia Cancer Registries and 100 AA from
Detroit to determine their exposure to structural racism stressors, which we will correlate with data from the
whole-genome sequencing (WGS) of their tumor tissue. Our aims are to: (1) determine the extent to which
exposure to structural racism over time is linked with differences in NSCLC tumor evolution by characterizing
the types of mutations, the order of their acquisition, and the activity of mutational processes; (2) define the
effect of structural racism stressors on early recurrence (within 2 years of surgery) in stage I-II AA NSCLC
patients and (3) determine the distribution of the genomics of never-smoking AAs with NSCLC compared to the
Sherlock-Lung study and if this distribution is affected by the stressors of interest. This innovative study will be
one of the first to use WGS, tumor evolution, and geospatial analysis techniques to identify causal pathways
linking structural racism stressors to the mutagenic processes of NSCLC, providing a much-needed integration
of social science with molecular outcomes. We expect that the structural racism stressors will induce
differences in timing of driver mutation development that promote early NSCLC recurrence. This study will
elucidate how racism-related socio-environmental factors affect AA NSCLC biology, which is expected to
reveal the mechanisms underlying disparate race-based NSCLC outcomes, ultimately leading to identification
of new targets and development of novel interventions to reduce health disparities.
