Etiology and Tumor Characteristics of Early-onset Pancreatic Cancer - Project Summary/Abstract Pancreatic cancer is the third leading cause of cancer-related death in the United States, with a dismal 5-year survival rate of 12%. While half of pancreatic cancers are diagnosed after age 70, the impact of younger cases is significant due to the loss of potential life years. In recent decades, there has been a steady increase in pancreatic cancer incidence among younger populations, yet the reasons for this trend remain unclear. Consid- ering the concurrent increase in obesity and early-onset pancreatic cancer, investigating the role of body fatness is crucial to understanding the growing burden of this disease. Furthermore, there are gaps in our knowledge regarding the clinicopathologic and molecular characteristics of early-onset pancreatic cancer compared to later- onset disease, as well as the influence of modifiable factors on these characteristics. This proposal aims to identify modifiable factors associated with the development of early-onset pancreatic cancer and characterize the clinicopathologic and molecular features of tumors in affected patients. Aim 1 will investigate the associations of early-onset pancreatic cancer with early-life body fatness, behaviors that prevent or mitigate obesity, and prediagnostic circulating markers related to obesity pathways. Aim 2 will compare the clinicopathologic, genomic, transcriptional, and tumor immune microenvironment characteristics between early-onset and later-onset pan- creatic cancer, with an additional exploration of the impact of tobacco smoking on these characteristics. To achieve these goals, I will leverage the resources of multiple population-based US cohort studies and pancreatic cancer patient cohorts. By elucidating the etiology of early-onset pancreatic cancer and providing insights into its distinct tumor characteristics, this research has the potential to inform prevention and treatment strategies, ultimately reducing the incidence and mortality of this highly lethal malignancy. As an experienced epidemiologist, this career development award will provide me with the opportunity to enhance my skills in interdisciplinary can- cer research, combining epidemiology with bioinformatics, data science, and molecular cancer. In the short term, my objective is to secure an independent, tenure-track faculty position at a prestigious institution where I can conduct innovative research focused on understanding the etiology and tumor characteristics of early-onset pan- creatic cancer. This career development award will serve as a solid foundation for my long-term aspiration of establishing a funded research program dedicated to cancer epidemiology and pancreatic cancer research, with the ultimate goal of reducing the burden of cancer.
