Health-related social needs, biological aging, and long-term mortality risk among a nationally representative cohort of cancer survivors.

542Background: Previous research has shown that individuals with unmet health-related social needs (HRSNs, such as food insecurity, unemployment, and inadequate or unstable health insurance coverage) experience accelerated biological aging. In this study, we examined the associations of HRSNs with long-term mortality risk among cancer survivors and the role of biological aging in mediating these associations. Methods: Cancer survivors aged 20-84 years were identified from the 1999-2010 National Health and Nutrition Examination Survey and linked with death certificate records through December 31, 2022. HRSNs, including poverty, lack of home ownership, food insecurity, unemployment, lack of health insurance, and coverage instability collected at interview, were categorized into a summary score indicating the number of present HRSNs. Biological aging was measured by the validated Phenotypic Age Acceleration (PhenoAgeAccel) based on clinical chemistry biomarkers, with accelerated aging defined as a value of > 0. Univariable and multivariable Cox proportional hazard models were fitted with age as time scale to examine the associations between HRSNs and all-cause and cancer-specific mortality risks, adjusting for demographic and clinical factors. PhenoAgeAccel was sequentially added in the models to calculate the percentage of each association mediated by accelerated biological aging. Results: The 715 survivors were aged 59.84 years at interview on average, and experienced 0.14 years (95%CI: 0.03-0.25) of accelerated biological aging. Survivors with certain characteristics had accelerated biological aging: male, non-Hispanic Black, low educational attainment, presence of HRSNs, smoking, obese status, having ≥3 comorbid conditions, or fair or poor health. In ≥20 years of follow-up, there were 315 deaths, including 103 from cancer. Among individual HRSNs, poverty and food insecurity were associated with a higher risk of any death, and lack of home ownership was associated with a higher risk of cancer death; these associations were attenuated more than 25% by adding PhenoAgeAccel in the models. In multivariable models, having ≥3 HRSNs was associated with increased risk of death (HR = 2.73, 95%CI = 1.45-5.14), 27% of which was attenuated by accelerated biological aging (HR = 2.26, 95%CI = 1.27-4.02). Conclusions: Both individual HRSNs and the number of HRSNs were associated with higher survivor all-cause mortality in a nationally representative cohort with two decades of follow-up; this may, in part, mediated by accelerated biological aging. Proactively addressing HRSNs may mitigate accelerated aging and therefore reduce mortality risk for cancer survivors. This study provides further evidence that investing in public assistance programs may reap many benefits to residents across the healthcare continuum.