Reducing racial disparities in lung cancer outcomes by decoding neighborhood contextual environment (RECODE)

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.