PROJECT SUMMARY / ABSTRACT The long-term goal of the K01 candidate, Dr. Trang VoPham, is to become an independent investigator in the epidemiology of environmental risk factors for liver disease using methods in geospatial science and health disparities. Dr. VoPham is a highly skilled epidemiologist and geospatial scientist and requires additional training in (1) liver disease epidemiology, (2) health disparities, and (3) electronic health record (EHR) analytics for her to become a successful independent researcher in liver disease. She has worked closely with her Mentors comprised of preeminent investigators in hepatology, disparities, epidemiology, and biostatistics: Dr. George Ioannou (Primary Mentor) and Co-Mentors, Drs. Jason Mendoza, Joel Kaufman, and Kristin Berry, to develop a comprehensive training and research program that builds on her research experience in liver cancer, epidemiology, and geographic information systems (GIS). Nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, and hepatocellular carcinoma (HCC), the most common type of primary liver cancer, are increasing in incidence worldwide. Recent evidence, including our preliminary data, show that ambient exposure to particulate matter less than 2.5 microns in diameter (PM2.5), a ubiquitous air pollutant, may increase NAFLD and HCC risk. Further, there is evidence suggesting that PM2.5 may differentially impact NAFLD and HCC risk in particular subgroups according to race/ethnicity, geography, and sex. Yet, to date, epidemiologic studies have been cross-sectional, limited to small study areas with little exposure variability, and/or did not adjust for potential confounders. EHRs are a valuable and underutilized resource for large-scale, prospective epidemiologic studies of time-varying environmental exposures, including rich information on residential address locations, clinical conditions, and demographics. Dr. VoPham proposes to fill these gaps in knowledge by examining the associations between ambient PM2.5 exposure and NAFLD risk (Aim 1) and HCC risk (Aim 2) and determining the role of PM2.5 on NAFLD and HCC incidence disparities by race/ethnicity, geography, and sex (Aim 3). The applicant will leverage the geographically expansive, racially and ethnically diverse Veterans Affairs (VA) patient population, conducting a state-of-the-science geospatial exposure assessment by linking VA patient geocoded residential addresses from EHRs with a high-resolution, validated PM2.5 exposure model using GIS. This interdisciplinary research will provide new insights into the potential role of PM2.5 as a novel, modifiable, biologically plausible risk factor for NAFLD and HCC, and as a potential environmental factor driving incidence disparities, providing translational insights to help identify individuals at high risk for liver disease. The world- class interdisciplinary expertise of the Mentoring Team, along with the outstanding supportive research environment at Fred Hutchinson Cancer Research Center, University of Washington, and VA Puget Sound Health Care System, will ensure that Dr. VoPham achieves all of her career development and research goals and will facilitate her transition to become a successful independent researcher in liver disease.

PROJECT NARRATIVE Nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, and hepatocellular carcinoma (HCC), the most common type of primary liver cancer, are increasing in incidence worldwide. Evidence suggests that exposure to fine particulate matter less than 2.5 microns in diameter (PM2.5), a ubiquitous air pollutant, may impact the risk of developing NAFLD and HCC, especially among particular subgroups defined by race/ethnicity, geography, and sex. We propose to investigate the associations between ambient PM2.5 exposure and NAFLD and HCC risk, and the contribution of PM2.5 to NAFLD and HCC incidence disparities, in veterans across the United States, which will help identify individuals at high risk for NAFLD and HCC.