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Principal Investigator: Sage J. Kim
Organization: UNIVERSITY OF ILLINOIS AT CHICAGO
Fiscal Year: 2024
Award: $603,011
Funding agency: National Institute on Minority Health and Health Disparities
ABSTRACT
This application proposes to examine a novel social epigenetic mechanism for racial inequality in lung cancer:
Reducing racial disparities in lung cancer outcomes by decoding neighborhood contextual environment
(RECODE). We will examine the relationships between exposure to violence, inflammatory responses,
smoking and epigenetic changes in protein arginine methyl transferases (PRMT6) that increase the risk of
developing lung cancer. Our preliminary studies demonstrated that smoking induces increased expression of
PRMT6 in the lung epithelium. We also showed that overexpression of PRMT6 triggers spontaneous lung
tumors in mice. Interestingly, we found that PRMT6 is upregulated among black men compared with white
men in The Cancer Genome Atlas (TCGA). Thus we argue that the increased overexpression of PRMT6
among black men may explain a higher rate of lung cancer among black men compared with white men. While
smoking is a key contributing factor for lung cancer, the frequency and amount of cigarette smoking are not
necessarily higher for blacks, which suggests that other factors are responsible for racial disparity in lung
cancer. Disproportionate social stress in black communities may be responsible for a higher rate of lung
cancer among blacks. In particular, individuals living in excessive neighborhood violence are exposed to
chronic stress, which may intensify the epigenetic changes for lung cancer. We hypothesize that exposure to
neighborhood violence is social stress that increases biophysical inflammatory responses, which exacerbate
the path between smoking, PRMT6 overexpression, and lung cancer.
To examine the proposed social epigenetic mechanism of lung cancer disparity, first, we will test the
independent effect of smoking and exposure to neighborhood violence, and the interaction of the two risks on
PRMT6 expression using retrospective tissue samples from black and white lung cancer cases (Aim 2).
Second, we will test the effect of exposure to violence on an inflammatory response (hair cortisol) and lung
cancer screening outcomes by conducting a prospective survey and data collection with high-risk black men
(Aim 3). Finally, we will build a multilevel, context-specific lung cancer risk profiles (Aim 1) that take into
account not only individual behavioral risk (smoking), but neighborhood stress (exposure to violence),
physiological inflammatory responses (increased cortisol), and molecular changes (PRMT6 overexpression).
To develop such risk profiles, we utilize a composite population data approach to establish accurate counts of
all individuals within census tracts with sociodemographic, behavioral, and neighborhood risk profiles.
The strength of RECODE is its innovative approach to unveil a social epigenetic mechanism of lung cancer
disparity. RECODE has the potential to transform understanding multilevel risks of lung cancer and improve
the national lung cancer screening guidelines to reflect the social conditions of racial minority communities.
Terms: <Aeroseb-HC><Affect><African American><African American group><African American individual><African American people><African American population><African Americans><Afro American><Afroamerican><Application Context><Area><Arginine><Behavioral><Biological><Biophysics><Black Populations><Black group><Black individual><Black people><Blacks><Cancer Cause><Cancer Etiology><Censuses><Cessation of life><Cetacort><ChIP Sequencing><ChIP-seq><ChIPseq><Characteristics><Chicago><Chronic><Chronic stress><Cities><Clinical Trials><Code><Coding System><Communities><Computerized Medical Record><Cort-Dome><Cortef><Cortenema><Cortisol><Cortispray><Cortril><Cotinine><Crime><Data><Data Collection><Data Set><Death><Death Rate><Dermacort><Disadvantaged><Disparities><Disparity><Distress><Economics><Eldecort><Electronic Medical Record><Environment><Environmental Factor><Environmental Risk Factor><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Epithelium><Exposure to><Frequencies><Gene Expression><Hair><Hydrocortisone><Hydrocortone><Hytone><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Incidence><Individual><Inflammatory Response><L-Arginine><Link><Low Prevalence><Lung><Lung Neoplasms><Lung Respiratory System><Lung Tumor><Malignant Tumor of the Lung><Malignant neoplasm of lung><Measures><Mediating><Methylation><Mice><Mice Mammals><Molecular><Morbidity><Morbidity - disease rate><Murine><Mus><Neighborhoods><Nutracort><Outcome><Patients><Physiologic><Physiological><Population><Proctocort><Protein Overexpression><Proteins><Pulmonary Cancer><Pulmonary Neoplasms><Pulmonary malignant Neoplasm><RNA Seq><RNA sequencing><RNAseq><Research><Risk><Risk Factors><Sampling><Scotine><Smoking><Smoking History><Social Conditions><Societal Conditions><Source><Stage at Diagnosis><Stress><Survey Instrument><Surveys><TCGA><Testing><The Cancer Genome Atlas><Time><Tissue Sample><Transferase><Transferase Gene><United States><Violence><biobank><biologic><biophysical foundation><biophysical principles><biophysical sciences><biorepository><black male><black men><cancer disparity><cancer health disparity><cancer risk><cancer-related health disparity><chromatin immunoprecipitation-sequencing><cigarette smoking><cigarette use><community violence><contextual factors><disparities in race><disparity due to race><disparity in cancer><economic><environmental risk><epigenetically><exposure to violence><high risk><high risk group><high risk individual><high risk people><high risk population><improved><in silico><inequality due to race><inequity due to race><innovate><innovation><innovative><lung cancer><lung cancer early detection><lung cancer screening><men><minority communities><mortality><mortality rate><mortality ratio><neighborhood violence><novel><overexpress><overexpression><pack/year><prospective><protein expression><pulmonary><race based disparity><race based inequality><race based inequity><race disparity><race related disparity><race related inequality><race related inequity><racial disparities in health><racial disparity><racial health disparity><racial inequality><racial inequity><racial minority><racially unequal><recommended screening><screening><screening guidelines><screening recommendations><screenings><segregation><social><social stress><social stresses><social stressor><socially stressed><socio-demographics><sociodemographics><socioenvironmental factor><systemic inflammation><systemic inflammatory response><transcriptome sequencing><transcriptomic sequencing><violence against communities><violence exposure><violent><violent behavior><violent crime>