FY23 Germline and Environmental Factors Associated with Pediatric Brain and Central Nervous System Tumors in Kentucky

Project Summary/Abstract Pediatric brain and central nervous system tumors (PBCNST) are the most common solid tumors and are the leading cause of disease-related death in United States (U.S.) children. PBCNST incidence rates in Kentucky are significantly higher than in the U.S. as a whole and are even higher among Kentucky’s Appalachian children. To understand and eventually eliminate such cancer disparities among Kentucky children, population-based research is needed to gain a thorough understanding of the epidemiology and etiology of the disease. Our team is currently engaged in a successful Kentucky Pediatric Cancer Research Trust Fund population-based study to identify factors associated with the high incidence of PBCNST in Kentucky. The current study leverages the infrastructure provided by the Kentucky Cancer Registry (KCR), its Virtual Tissue Repository and the NIH Kids First Data Resource Center (DRC) with the specific aims to: 1) to identify potential environmental exposures associated with Kentucky’s high rates; 2) to assess whether Kentucky-specific mutations and mutational signatures exist that may be related to PBCNST, and to determine whether known genetic risk factors for PBCNST are present among Kentucky children; and 3) implement informatics infrastructures for data sharing with national PBCNST consortia. Initial findings from this study have reaffirmed evidence of significantly high PBCNST rates in a 37 county region of central and Appalachian Kentucky. This subsequent study proposes to expand upon the depth and breadth of the PBNCST data through the collection of non-cancerous specimens, environmental samples, and information directly from the PBCNST survivors and their families. Specific aims of this study are to 1) enhance the retrospective population-based molecular and clinical data with germline sequencing and analyses; 2) fully characterize potential environmental, lifestyle and genetic risk factors through patient and family interviews; and 3) incorporate the additional data and enhance data sharing infrastructures in collaboration with the Children’s Hospital of Philadelphia (CHOP) and the NIH Kids First Data Resource Center (DRC). The first aim will involve contact and recruitment of cancer survivors from the original study to request the donation of germline (normal) cells through saliva collection kits to be sequenced by the Children’s Hospital of Philadelphia (CHOP). Germline data will significantly enhance our ability to identify and distinguish genetic markers that may have increased the risk of developing these tumors. It will also allow us to more clearly delineate mutational changes specific to the tumors that have already been sequenced. The second aim…. (Erin/Ellen) The third aim will expand the Kentucky Cancer Registry Cancer Research Data Commons to include additional data and enhance the data sharing portal to make the new data accessible to researchers for current and future studies. The proposed enhancements promote a deeper understanding of these tumors and risk factors and may further elucidate opportunities for screening and preventative measures for Kentucky and other children.