Abstract A009: Association of neighborhood disadvantage with biomarkers of biological aging and chronic stress among breast cancer survivors. [R]
Authors: Shen Jie , Zhao Hua , Fuemmeler Bernard , Sheppard Vanessa , Bear Harry 
Published: January 2023

Abstract
Living in a disadvantaged neighborhood is associated with adverse outcomes among breast cancer patients, but the underlying pathway is still unclear. Limited evidence has suggested that chronic stress and accelerated biological aging may play an important role. Biological aging and chronic stress are closely related, and both associated with mitochondrial dysfunction, abnormal DNA methylation, telomere shortening, etc. For example, allostatic load (AL), a biomarker of chronic stress, increases with age as a result of the cumulative effects of allostasis across the lifespan. In this study, we attempted to take the first step by evaluating the association of neighborhood disadvantage with biomarkers of chronic stress and biological aging among breast cancer patients. Using a sub-sample of 906 women with newly diagnosed breast cancer at M.D. Anderson, we examined whether levels of AL and selected biological aging biomarkers (global DNA methylation, telomere length, etc.) were affected by neighborhood disadvantage. The Area Deprivation Index (ADI) was used to measure the levels of neighborhood disadvantage. Telomere length and global DNA methylation in leukocytes were measured by qPCR and ELISA, respectively. We used 17 factors that represent the activity of five physiological systems to construct the AL score. Based on the median ADI at the national level, the study population was divided into low and high ADI groups. Overall, breast cancer patients from the high ADI group were more likely to be younger and non-Hispanic Black than those from the low ADI group (P&lt;0.001). They were also more likely to have higher stage and poorly differentiated breast tumors (P=0.029 and 0.019, respectively). For the relationship with markers, compared to the low ADI group, high ADI group had higher median levels of AL (P=0.046) and lower median levels of global DNA methylation (P&lt;0.001). Higher AL was considered as an indicator of increased chronic stress. Compared to their counterparts, those from the high ADI group were 20% and 32% more likely to have increased AL and telomerase activity, respectively, and 51% less likely to have increased levels of global DNA methylation. We also found that ADI was inversely correlated with telomere length. Additionally, we found that the significant associations of AL and global DNA methylation with ADI group were observed in non-Hispanic Whites and Blacks, but not in Hispanics. Lastly, using the mediation analysis, we found that decreased global DNA methylation mediated 6.52 and 7.98% of the association between higher ADI group with stage III and poorly differentiated tumor (P=0.037 and 0.023), respectively. In summary, we observed that neighborhood disadvantage was associated with more aggressive breast tumor characteristics, and influenced the levels of AL and global DNA methylation among breast cancer patients. Our findings suggest that neighborhood disadvantage is biologically embedded in molecular level and associated with accelerated biological aging and increased chronic stress among breast cancer patients.
Citation Format: Jie Shen, Hua Zhao, Bernard Fuemmeler, Vanessa Sheppard, Harry Bear. Association of neighborhood disadvantage with biomarkers of biological aging and chronic stress among breast cancer survivors. [R] [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A009.