PROJECT SUMMARY / ABSTRACT The candidate's long-term career goal is to become an academic leader in “precision cancer prevention”, by linking clinical and epidemiological risk factors with novel molecular markers, and applying decision and implementation tools to direct heathcare resources to the most effective and practical prevention strategies in the appropriate risk groups. The U.S. Preventive Services Task Force (USPSTF) recently released new recommendations supporting the use of low-dose aspirin for the primary prevention of CRC and CVD in adults aged 50-59 with certain CVD risk profiles. However, evidence for the efficacy of daily low-dose aspirin use among older people are lacking, and net benefits were not considered in the context of baseline CRC risk. In addition, impact and challenges in implementing the 2016 USPSTF guideline, and potential more refined precision-based recommendations have not been investigated. Building on the candidate's passion to bridge evidence with policy to improve practice in real world settings, as well as her prior research experience in cancer epidemiology and aspirin chemoprevention, the candidate seeks to fill these knowledge gaps through this novel and high impact research project to 1) examine the overall benefits and harms of low-dose daily aspirin use in a large randomized controlled trial among adults aged 65 and above, and estimate aspirin's efficacy on CRC according to CRC screening and baseline CRC risk predicted by clinical and genetic susceptibility (Aim 1); 2) refine the net benefits of low-dose aspirin use among adults aged 50 and above according to both CRC and CVD risk integrating findings from the RCT and stratified analyses using decision modeling (Aim 2); 3) examine the impact of 2016 USPSTF recommendations using national survey, and identify the barriers and facilitators for implementation at provider and patient level through interviews (Aim 3). The candidate will develop the necessary skills to conduct this work through a multidisciplinary mentoring committee, consisting of internationally recognized experts in cancer prevention and implementation science (Dr. Graham Colditz), aspirin chemoprevention (Dr. Andrew Chan), decision modeling (Dr. Ann Zauber), and health behaviors (Dr. Aimee James). The candidate will also receive committed mentorship from Dr. John McNeil at Monash University and Dr. Iris Lansdorp-Vogelaar from Erasmus MC, and collaborate with Dr. Nathan Moore from BJC Medical Group. In addition to mentored research, the candidate will also benefit from formal training through didactic coursework, attendance at scientific meetings, publication in peer-reviewed journals, and submission of an R01 grant. This mentoring and in-depth training in decision science and implementation science as well as national and international collaborations, will be critical for the candidate to develop new, interdisciplinary, and unique areas of expertise, and establish a strong research network...