Socio-environmental Factors, Accelerated Aging, and Cancer Risks and Outcomes in Middle-Aged and Older Adults - Persistent differences in cancer incidence, mortality, and survival across population subgroups cannot be explained fully by traditional risk factors. These differences are seen for all cancers combined, most common cancers, frailty, morbidity, and mortality among cancer survivors. Complex interactions of biologic, psychosocial, socioeconomic, and environmental factors contribute to these differences. This project, responsive to PAR-23-255, will use data from two well-characterized prospective studies, the Atherosclerosis Risk in Communities (ARIC) Study and Multi-Ethnic Study of Atherosclerosis (MESA), to investigate contributions of person-level and neighborhood-level social and structural determinants of health (SSDOH) to accelerated biological aging, cancer risk, and differences in frailty and mortality among cancer survivors. We will examine independent and joint contributions of education, economic stability, social isolation and support, neighborhood demographics and area deprivation ascertained at the census tract level, to study outcomes. This proposed study builds on our existing work (R01CA267977) that has used published and novel proteomic aging clocks (PACs) to quantify biologic aging and link PAC acceleration to total cancer risk, risk of smoking-related cancers, and frailty and mortality in cancer survivors in ARIC and MESA. With this R21, we seek to better understand the SSDOH drivers of age acceleration and their contribution to cancer risk and survivorship. By examining person-level and neighborhood-level SSDOH measures, we aim to address the complexity of variations in cancer incidence and survivorship. We have SSDOH, proteomic and cancer data on >10,800 ARIC participants with nearly 4,100 incident cancer cases over 30 years of follow-up, and >5,300 MESA participants with nearly 700 incident cancer cases over 18 years of follow-up. Our central hypothesis is that SSDOH become biologically embodied via PAC acceleration leading to disparities in cancer risk and survivorship outcomes. Specific Aims are: 1) Identify associations of person-level and neighborhood-level SSDOH with PAC acceleration and incident cancer in two prospective cohorts of adults. 2) Determine associations of both person-level and neighborhood-level SSDOH with PAC acceleration, frailty, and all-cause mortality among cancer survivors in ARIC and MESA. Our proposed analyses will be completed in the total population of ARIC and MESA (separately) and then stratified by population subgroups; subsequently we will complete meta-analyses combining ARIC and MESA data. Our multi-disciplinary study team is well-prepared to lead this work, with complementary expertise in research on population health differences, SSDOH and chronic disease risk, molecular and cancer epidemiology, oncology and cancer survivorship, aging biomarkers, biostatistics, and proteomics analyses. The proposed study will have a significant impact by advancing the understanding of how socio-environmental factors translate into biological age acceleration, measured by PACs, and lead to greater cancer risk and adverse outcomes among cancer survivors.
