Abstract 1195: Measuring the biological effects of structural racism on aging and cancer outcomes in the U.S

Abstract The impact of structural racism (SR) on health has garnered more attention, as more reliable techniques to accurately measure SR are generated and validated. SR is the systematic fostering of racial discrimination through mutually reinforcing systems such as housing, healthcare, criminal justice, education, and others. It has been linked to negative impacts on health, including adverse cancer outcomes. There remains a large gap, however, regarding how SR is biologically linked to these adverse outcomes. Given the plasticity of the epigenome to environmental factors, it is plausible that the negative impacts of SR may lead to epigenetic differences that may impact health. Additionally, the chronic stress associated with living in areas of high SR may negatively impact epigenetic aging and disease prevalence. Here, we aim to quantitatively analyze the effects of SR on human disease by determining associations between a U.S.-based SR index, accelerated aging, race, and disease prevalence through secondary data analysis. Our cross-sectional study consists of 13,919 men and women from the TruDiagnostic® methylation database, who live in the U.S., provided informed consent, zip code data, race/ethnicity data, are >18 years old, and donated a blood specimen for methylation testing via the EPIC850K array. We used the structural racism effect index (SREI) for this study, a national multi-level index that measures the approximate socioeconomic position of neighborhoods based on 9 Census-tract domains including built environment, criminal justice, education, employment, housing, income and poverty, social cohesion, transportation, and wealth. Study participants were linked to the SREI using 5-digit U.S. zip codes. Structural racism was significantly different among the 4 racial and ethnic groups (AfAm/Black, Asian, European, Latino/Hispanic) with Asian individuals experiencing the least amount of SR and Hispanic/Latino and AfAm/Black individuals experiencing the most. As quartiles, SR was associated with accelerated epigenetic aging using the Hannum, Horvath, Grim, and PhenoAge epigenetic aging measures. Increasing SR quartiles were associated with increased odds of any cancer (Q1(ref) v Q4 odds ratio [OR] = 1.24, 95% CI [1.03, 1.49]), in addition to other disease outcomes including odds of any reproductive disease (Q1 v Q4 OR = 1.35, 95% CI [1.14, 1.60]), and any skin/hair condition (Q1 v Q4 OR = 1.18, 95% CI [1.05, 1.33]). Using this data, we will link individual CpG sites and differentially methylated regions (DMR) to the SREI using regression modeling, DMR analysis, and pathway analysis. SR is multi-faceted and challenging to measure accurately, but limited studies have established a clear relationship between SR and negative health effects. This study will be one of the first to connect a SR index with biological mechanisms that impact disease risk, and we hope our efforts will expand future studies in this area. Citation Format: Brittany D. Jenkins, Sebastian Z. Ramos, Lauryn Martin, Avonne E. Connor. Measuring the biological effects of structural racism on aging and cancer outcomes in the U.S [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1195.