Abstract 2163: Socioeconomic status associates with epigenetic modulation of TET2: An emerging pathway in cardio-oncology

Abstract

Abstract Introduction: Adverse social determinants of health (SDOH) are known to accelerate poor outcomes in cardiovascular disease (CVD) and cancer. Clonal Hematopoiesis (CH) is a mechanism implicated in these disease states, partially driven by epigenetic regulatory genes, including TET2. Yet, there is not much known about how epigenetic modulations of TET2 itself may relate to the immune system and subsequent disease development. Hypothesis: We hypothesize that socioeconomic status (SES), as a SDOH marker, relates to epigenetic modulation of TET2. Methods: 60 African American adults (93.3% female, mean age 61) with CVD risk, living in the Washington, D.C. area self-reported their SES as household income. Immune system activity was assessed via splenic activity (SpleenA) by 18FDG PET/CT. Serum cytokine levels were measured by ELISA and DNA methylation analysis evaluated the epigenetic modulations of TET2. Multivariable regression analysis adjusted for ASCVD 10-year risk score and BMI was used to examine associations. Results: Out of 33 TET2 methylation sites, we found 3 sites that were significantly related to SES. Notably, only Tet2cg09666717 (SES β=0.310, p=0.038) was also associated with SpleenA (β=-0.453, p=0.036) and several cytokines: IL-17A, IL-1β and TNFα along with trending to significance with IFN-γ (Table). Conclusion: Thus, we found that SES associates with hypomethylation of Tet2cg09666717, which further related to SpleenA and inflammatory markers. Our findings are hypothesis generating and suggest that lower SES may relate to inflammation and immune system dysregulation by the way of epigenetic modulation of TET2. These results should be examined in larger, functional studies with diverse population-based cohorts to determine the potential relationships of both SDOH and epigenetic markers in CH and cardio-oncology outcomes. Associations between TET2 methylation sites, SpleenA, SES and Cytokines in DCCNHA cohort, 2014-17 Tet2cg09666717 Tet2cg05094833 Tet2cg10594473 SES 0.310 (0.038) -0.405 (0.006) -0.283 (0.060) Splenic Activity -0.453 (0.036) 0.004 (0.985) 0.097 (0.654) IL-6 -0.078 (0.558) -0.211 (0.108) -0.222 (0.084) IL-8 -0.199 (0.153) 0.024 (0.865) -0.004 (0.979) IL-17A -0.373 (0.010) 0.134 (0.370) -0.434 (0.017) IL-1β -0.382 (0.003) 0.042 (0.757) -0.143 (0.275) TNFα -0.456 (0.000) -0.157 (0.244) 0.005 (0.969) IFN-γ -0.258 (0.062) -0.037 (0.790) 0.022 (0.876) Data are presented as standardized β coefficient (p-value). All data are adjusted for 10-year predicted ASCVD risk and BMI; ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; IL-6 = interleukin 6; IL-8 = interleukin 8; IL-17A = interleukin 17A; IL-1β = interleukin 1 beta; TNFα = tumor necrosis factor; IFN-γ = interferon gamma Citation Format: Sonal Sharda, Yvonne Baumer, Alina P. Pang, Abhinav Saurabh, Billy S. Collins, Valerie M. Mitchell, Michael J. Corley, Tiffany M. Powell-Wiley. Socioeconomic status associates with epigenetic modulation of TET2: An emerging pathway in cardio-oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2163.