Neighborhood Deprivation DNA Methylation in breast tumor tissue: Exploring the Interconnectivity between race, socioeconomic disadvantage, and cancer epigenetics Restricted; Files Only

Abstract

Further research is needed to understand why Black women are disproportionately affected by breast cancer despite similar screening rates as other racial and ethnic groups. Neighborhood deprivation, a measure of socioeconomic conditions, significantly impacts health and well-being. This study evaluates the association between neighborhood deprivation and DNA methylation in breast tumor tissue.

We analyzed 80 Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) women who were diagnosed with a first-primary stage I, II, or III BC, and underwent surgery at Emory University Hospital, Emory University Hospital Midtown, and Grady Memorial Hospital. NDI was constructed using the 2015 Area Deprivation Index (ADI) sourced from the Neighborhood Atlas, and data from the 2011–2015 American Community Survey (ACS) for census block groups in Georgia.

DNA methylation was assessed in breast tumor tissue using the Illumina Infinium MethylationEPIC 850K Beadchip. Epigenetic age was calculated using R’s methylclock package. Linear regression models evaluated the association between neighborhood deprivation and DNA methylation, adjusting for covariates. Cox proportional-hazards models examined associations between CpG sites related to neighborhood deprivation and all-cause mortality.

In the epigenome-wide analysis examining the relationship between the exposure and outcome no CpG sites met the threshold for FDR significance after adjusting for multiple comparisons (FDR<0.10). Neighborhood deprivation was associated with non-significant changes in epigenetic age acceleration in both Hannum and Horvath clocks. To our knowledge, this study among the first to assess the association between this specific neighborhood deprivation index, DNAm in breast tumor tissue, and epigenetic age acceleration. While our study did not find a direct link between neighborhood deprivation and DNA methylation in breast tumor tissue emerging evidence suggests that neighborhood disadvantage, shaped by structural racism, influences DNA methylation patterns, biological aging, and breast cancer mortality. Our data emphasize the need for larger, well-powered studies to better understand the connection between systemic inequities and cancer-related epigenetic alterations.

Table of Contents

Table of Contents

Literature Review.. 1

Introduction. 1

Main Associations between Neighborhood Deprivation and Breast Cancer 3

Neighborhood deprivation’s impact on health. 3

Impact of race on differential DNA Methylation. 5

Impact of epigenetic age on differential DNA Methylation. 6

Impact of Area-level socioeconomic deprivation indices on differential DNA Methylation. 7

Impact of neighborhood deprivation indices 8

Main associations between redlining and BC. 9

Impact of Redlining and Lending Bias on Health. 9

Associations between deprivation, redlining, and DNA Methylation. 10

Conclusion. 11

Introduction. 12

Methods 14

Study population. 14

Exposure assessment 15

Outcome assessment 15

DNA Methylation. 16

Covariates 16

Calculation of epigenetic age. 17

Statistical Analysis 17

Results 18

Discussion. 19

Conclusion. 22

Future Directions 23

Tables and Figures 24

Table 1: Patient demographic and clinicopathologic characteristics among 80 NHB and NHW women diagnosed with stage I to III breast cancer in metropolitan Atlanta between 2010–2014. 24

Table 2 Association between neighborhood deprivation and epigenetic acceleration (1) age, and (2) age and race. 26

Figure 1 CONSORT. 27

Figure 2 DAG.. 28

Figure 3 Epigenetic age estimation assessing the relationship between DNA methylation age and chronological age using Horvath's method. 29

Figure 4 Epigenetic age estimation assessing the relationship between DNA methylation age and chronological age using Hannum’s method. 30

References 31

About this Master's Thesis

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School	Rollins School of Public Health
Department	Executive Masters of Public Health - MPH
Subfield / Discipline	Applied Epidemiology
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Keyword	Neighborhood deprivation Epigenetics DNA Methylation Socioeconomic status Racial disparity Epigenome Breast Cancer Epigenetic Age Acceleration Breast Cancer Mortality
Committee Chair / Thesis Advisor	Lauren McCullough, Emory University
Committee Members	Jasmine Miller-Kleinhenz, Emory University Lauren Barber, Emory University

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