PNETs are cancers that arise from hormone-producing cells of the pancreas. They are usually diagnosed in late stages, with few treatments available. PNETs are the second most common pancreatic cancer and are rapidly increasing in incidence. Black pNET patients have worse survival and higher rates of cancer spread associated with smaller tumors than White patients. These clinical disparities suggest a biologic difference between these two patient groups. Guidelines for treating pNETs are mostly based on data from White patients and may not apply to Black patients. Differences in cancer biology between racial groups that affect disease severity has been discovered in other cancers. Notably, there are differences in epigenetic modifications between different ethnic and racial groups. Epigenetic regulation of gene expression, including DNA methylation (whereby chemical groups are added to DNA to alter the generation of gene product), is an important mechanism by which environmental factors, lifestyle, and stress can affect an individual’s genes. pNETs are known to have high rates of epigenetic dysregulation. However, nothing is known about the differences in the (epi)genetics of pNETs between Black and White patients, as Black patients represent under 1% of patients included in genetic studies of pNETs. Other key differences may exist between how tumor from different patient populations interact with the normal tissue environment or the patient’s immune system. The goal of this project is to investigate the causes of the clinical outcomes differences between Black and White patients with pNETs. These differences may be at the (epi)genetic level, how the tumor interacts with surrounding cells, or environmentally influenced. The proposed research will compare the genomes and gene regulation systems between the two patient groups to find what is driving the clinical differences seen at a cellular level. This will demonstrate if the clinical outcome differences could be due to how the body keeps the tumor at bay and determine what key stressors exist today in the Black pNET patient population in the Deep South. While this study is aimed at understanding the ways in which epigenetic and gene expression changes affect pNETs in Black patients, the findings will profoundly impact the direction of both pNET treatment and research for the entire patient population.