Abstract Disclosure: H. Heath: None. S. Kim: None. Z. Madak Erdogan: None. Despite smoking less, Black men experience a higher incidence of lung cancer than white men. This health disparity is even more prevalent in Black men from Chicago, suggesting local neighborhood factors impacting tumorigenesis. Preliminary data found that Black men compared to white men exhibit overexpression of the epigenetic regulator known as PRMT6, have elevated levels of hair cortisol, and live in neighborhoods with disproportionately high levels of violence. This research aims to investigate the receptor for cortisol called glucocorticoid receptor (GR), and PRMT6 recruitment to chromatin and to correlate this recruitment with tumor cortisol levels and exposure to neighborhood violence. Using a version of ChIP-sequencing known as CUT & RUN, the gene binding sites of PRMT6 and GR will be identified using 16 lung tumor samples from patients living in Chicago. Cortisol levels present in lung tumors will be detected using LC-MS. These cortisol levels will be correlated with GR and PRMT6 recruitment to chromatin and neighborhood homicide data obtained using patients’ zip codes. We hypothesize that PRMT6 and GR will be recruited to regulatory regions of genes related to increased lung tumor aggressiveness. We also anticipate that cortisol levels will correlate with neighborhood violence levels and elevated PRMT6 and GR colocalization, indicating chronic exposure to stress as a regulator of lung tumor formation. Presentation: Thursday, June 15, 2023