PROJECT SUMMARY - CANCER EPIDEMIOLOGY, PREVENTION AND CONTROL (CEPaC) The CEPaC program plays a central role in the scientific, clinical and public health mission of AECC, and is the focal point for the translation of laboratory-based research into studies at the population level. The broad aims of CEPaC are to conduct studies in human populations to determine the behavioral, environmental and molecular etiologic risk factors that underlie cancer development and outcomes, (especially actionable targets for screening, prevention, and treatment), and further, to implement interventions and test their effectiveness in the community. CEPaC has long been recognized for its contributions to the study of HPV and to molecular epidemiologic cancer research. However, in recent years, cancer prevention and control research has greatly expanded, with a strong focus on the largely poor and minority Bronx population. CEPaC is organized into four major themes: (i) Infectious Risk Factors, including oncogenic HPV, HIV, HCV, and the human microbiome; (ii) Hormonal, Obesity, and Inflammation-Related Risk Factors; (iii) Genetic/Epigenetic Risk Factors; and (iv) Cancer Prevention, Control, and Implementation Science, encompassing prevention, health care delivery, health disparities, survivorship and outcomes, especially in the local catchment area. CEPaC research has also been impactful on clinical guidelines and practice, and recent studies will maintain this trend. For example: (i) CEPaC laboratory advancements led to the characterization of HPV sub-lineages and HPV DNA methylation, both sufficiently associated with strong risk of cervical cancer and precancer with the potential to improve the positive predictive value (PPV) of recently FDA-approved ?primary HPV screening?; (ii) obese women with normal insulin levels were shown to have no greater risk of incident post-menopausal breast cancer than normal weight women with normal insulin, but those with elevated insulin had significantly increased risk regardless of obesity status ? results that demonstrate the importance of etiologic biomarkers in risk stratification (e.g., versus obesity), characterizing possible carcinogenic pathways, and as targets for chemoprevention; (iii) a novel signature of metastatic risk based on laboratory and animal model studies was strongly associated with metastasis of ER+/HER2- tumors in postmenopausal women, and may have a role in guiding treatment decisions; (iv) firefighters who worked at the 9/11 WTC disaster site were found to be at increased risk of developing MUGUS, a precursor of multiple myeloma, leading to changes in monitoring practices in this group. Finally, the recent Einstein/Montefiore merger has increased shared interest in collaborative cancer prevention initiatives in the Bronx, including community needs assessment, defining cancer-health priorities, community outreach, and studies of the impact of these initiatives. There are 30 program members from 14 departments. Current NCI funding is 7.7M (direct); total peer-reviewed funding is 10.9M (direct). There have been 811 publications since July 2013 of which 31% represent intra-programmatic, 14% inter-programmatic, and 62% represent collaborations with investigators at other institutions.