Survivors of cancers diagnosed in adolescence or young adulthood have an elevated risk of multiple health problems. They also experience specific and unique psychosocial stressors and life disruptions having ramifications for their health, mental health, and quality of life (QOL). These outcomes, and disparities in these outcomes (by race/ethnicity, sex and gender, geographic location), may be largely a function of social determinants of health, including socioeconomic gradients, exposures to early childhood traumas or adversity, and accumulated experiences of discrimination. Yet, little is known about these effects including the biological pathways through which the known effects of social-environmental risk factors on population health and well-being influence outcomes in post-treatment AYA cancer survivors, particularly with regard to morbidity, mortality, and QOL. Therefore, the research proposed here is intended to identify and define functional genomic pathways through which current and past psychosocial and social environmental risk and resilience factors influence gene regulation in AYAs, and thus contribute to a greater understanding of health disparities in post-treatment survivorship. We propose a 5-year longitudinal prospective cohort study of 2000 AYA cancer survivors recruited within one year following completion of treatment for Hodgkin or non-Hodgkin lymphomas. Using repeated measures of risk and resilience factors and blood assays, we will evaluate the extent to which biological, psychological and social indicators are associated with, and potentially predict, mortality and morbidity in AYA cancer survivors within two years following completion of therapy. In collaboration with the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) research infrastructure and the National Cancer Institute Community Oncology Research Program (NCORP), this study will 1) identify the genome-wide transcriptional impact of social-environmental RISK factors (i.e., adverse living conditions/poverty, childhood trauma exposure, social isolation, and discrimination) and define the relationships of those genomic profiles to AYA survivor mortality, morbidity, and QOL; 2) identify the genome-wide transcriptional impact of individual RESILIENCE factors (i.e., social support, sense of purpose/meaning-making, self-efficacy) and define the relationships of those genomic profiles to AYA mortality, morbidity, and QOL; and, 3) identify the genome-wide molecular correlates of vulnerable populations, as structured by race/ethnicity, sexual/gender identity, and geography (e.g., rural vs. urban), and define the relationships of those genomic profiles to AYA survivor mortality, morbidity, and QOL. The study results may inform the conceptualization and development of new biological / molecular targets for future interventions to reduce risks for long-term and late effects of treatment and maximize likelihood of long-term health and QOL for AYA cancer survivors.