Reducing lung cancer by decoding the link between neighborhood exposure and biological responses (RECODE)

University Of Illinois At Chicago, Chicago IL

Investigators

Linked publications, trials & patents

Abstract

ABSTRACT This application proposes to examine a novel social epigenetic mechanism for lung cancer: Reducing lung cancer by decoding the link between neighborhood exposure and biological responses (RECODE). We will examine the relationships between exposure to neighborhood stress, smoking, inflammatory responses, 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. We argue that the increased overexpression of PRMT6 may explain a higher rate of lung cancer. While smoking is a key contributing factor for lung cancer, the frequency and amount of cigarette smoking are not necessarily higher among population groups with higher lung cancer rates, which suggests that other factors are responsible for lung cancer risk. Neighborhood stress exposure may be responsible for a higher rate of lung cancer. In particular, individuals living in neighborhoods with high levels of crime/violence are exposed to chronic stress, which may intensify the epigenetic changes for lung cancer. We hypothesize that exposure to neighborhood violence increases biophysical inflammatory responses, which exacerbate the path between smoking, PRMT6 overexpression, and lung cancer. To examine the proposed epigenetic mechanism of lung cancer, 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 of 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 (Aim 3). Finally, we will build 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 synthetic population 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 unveiling a social epigenetic mechanism of lung cancer risk. RECODE has the potential to transform understanding of multilevel risks of lung cancer and improve the national lung cancer screening guidelines to reflect stress exposure and epigenetic changes that may increase the risk of developing lung cancer.