Abstract 6128: Association between neighborhood disinvestment and all-cause survival moderated by epigenetic age among women with breast cancer
Authors: Plascak Jesse J. , Archer Kellie , Llanos Adana A. , Mooney Stephen J. , Xing Cathleen Y. , Rundle Andrew G. , Zarbl Helmut , Qin B , Zeinomar Nur , Schootman Mario , Yao Song , Ambrosone Christine , Pawlish Karen , Demissie Kitaw , Bandera Elisa V. , Hong Chi-Chen 
Published: March 2024

Abstract
Background: DNA methylation is hypothesized to mediate relationships between chronic social disadvantage and cancer outcomes. We investigated whether epigenetic age acceleration mediates the association between modifiable neighborhood disinvestment and survival within a cohort of women with breast cancer.
Methods: Individual-level data were from the Women’s Circle of Health Follow-up Study, a breast cancer cohort comprising women self-identifying as African American or Black, diagnosed 2013-2019 in New Jersey residents. Demographic, socioeconomic, health behavior, and dietary characteristics were self-reported. Peripheral blood samples from 312 participants collected 18-24 months after diagnosis were profiled for DNA methylation using Illumina’s MethylationEPIC array. After pre-processing, pace of biological aging was estimated using DunedinPACE. Neighborhood disinvestment was assessed using a previously validated virtual audit of 6 disinvestment indicators - garbage, graffiti, dumpsters, poor building conditions, poor yard conditions, abandoned buildings - in 14,671 Google Streetview streetscapes. Accelerated failure time models of all-cause mortality as functions of neighborhood disinvestment and pace of biologic aging were fit to estimate survival time ratios (TR), adjusted for stage at diagnosis and neighborhood socioeconomic composition using causal mediation analyses. End of follow-up was August 13, 2023.
Results: There were 46 all-cause deaths through follow-up (median=6.9 years), and 5-year overall survival probability was 0.90 (95% CI: 0.86, 0.93). Minimum, median, and maximum pace of biologic aging was 0.87, 1.26, and 1.72 indicating accelerated aging (&gt; 1.0) among most participants. There was no evidence for mediation of the neighborhood disinvestment - survival effect by pace of biologic aging (indirect effect p-value=0.33). There was evidence of an interaction between pace of biologic aging and neighborhood disinvestment in the adjusted model: survival time decreased 37% (95% CI: 4% - 59%, p=0.03) per 1 standard deviation (SD) increase in neighborhood disinvestment at pace of biologic aging values 1 SD below the average (&lt; 1.13). There was no evidence of such association at pace of biologic aging values 1 SD above the average (p=0.86).
Conclusion: Greater neighborhood disinvestment may be associated with shorter survival following a breast cancer diagnosis among those with slower than average epigenetic age acceleration, due to the cumulative nature of neighborhood disinvestment as a chronic indicator of social disadvantage.
Citation Format: Jesse J. Plascak, Kellie Archer, Adana A. Llanos, Stephen J. Mooney, Cathleen Y. Xing, Andrew G. Rundle, Helmut Zarbl, B Qin, Nur Zeinomar, Mario Schootman, Song Yao, Christine Ambrosone, Karen Pawlish, Kitaw Demissie, Elisa V. Bandera, Chi-Chen Hong. Association between neighborhood disinvestment and all-cause survival moderated by epigenetic age among women with breast cancer [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 6128.