Proposed Supplement Research Project: Elucidating individual and neighborhood factors associated with nonalcoholic fatty liver disease (NAFLD) Abstract: While overall cancer rates are declining in the United States (U.S.), liver cancer incidence has more than tripled in the last four decades, making it the fastest rising cancer in the U.S. Liver cancer mortality is the fifth and seventh leading causes of cancer death among men and women, respectively. Nonalcoholic fatty liver disease (NAFLD) affects about 30% of the U.S. adult population, has rapidly become a leading cause of chronic liver disease, and is increasingly recognized as an important risk factor for developing liver cancer. Identifying and mitigating exposure to potentially modifiable risk factors can reduce the morbidity and mortality related to long-term sequelae of NAFLD, including cirrhosis and liver cancer. Established risk factors for NAFLD include obesity, type 2 diabetes, older age, hypertension, dyslipidemia, and metabolic syndrome. Studies have suggested that neighborhood factors may be associated with NAFLD development and progression to liver cancer through insulin resistance and altered gut flora. However, no studies have examined the relationship between social and built environment attributes and NAFLD. We propose a prospective cohort study of approximately 2 million patients from three healthcare systems in California (UCSF Health System and San Francisco Health Network) and Hawaii (Kaiser Permanente Hawaii) to address these research gaps. Leveraging this racially/ethnically and socioeconomically diverse cohort, this proposed study will examine multilevel risk factors (social, behavioral, clinical, and neighborhood) associated with NAFLD, including identification of those with previously undiagnosed NAFLD. We will engage with the San Francisco Cancer Initiative (SFCAN), a local community partnership focused on reducing cancer burden in San Francisco, for interpretation and dissemination of results. Identifying individual- and neighborhood-level risk factors are relevant for future targeted interventions that will be critical to address these disparities.