Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors

• Type of Material: Article
• Authors: Brittany D. Jenkins, National Cancer Institute; Emily Rossi, National Cancer Institute; Catherine Pichardo, National Cancer Institute; William Wooten, University of Maryland, Baltimore; Margaret Pichardo, University of Pennsylvania; Wei Tang, National Cancer Institute; Tiffany H. Dorsey, National Cancer Institute; Anuoluwapo Ajao, Case Western Reserve University; ruby Hutchison, National Cancer Institute; Leah Moubadder, Emory University; Lauren McCullough, Emory University; Maeve Bailey-Whyte, National Cancer Institute; Stegan Ambs, National Cancer Institute
• Language: English
• Date: 2023-11-06
• Publisher: JAMA Network Open
• Publication Version: Final Published Version
• Copyright Statement: 2023 Jenkins BD et al. JAMA Network Open.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1001/jamanetworkopen.2023.41651
• Title of Journal or Parent Work: JAMA Network
• Volume: 6
• Issue: 11
• Start Page: e2341651
• Grant/Funding Information: This research was supported by grant ZIA BC 010887 from the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (Dr Ambs) and the National Cancer Institute Cancer Prevention Fellowship Program (Drs Jenkins and Rossi).
• Keywords: socioeconomic deprivation; neighborhood environment; breast tissue DNA methylation; Black and White women; breast cancer
• Research Categories: Health Sciences, Oncology; Health Sciences, Public Health

Abstract

Importance The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood. Objective To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer. Design, Setting, and Participants This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003. Participants were recruited through the University of Maryland Medical Center, with additional collection sites at Baltimore-area hospitals. Data analysis was performed from March 1 through December 1, 2022. Exposure Year 2000 census tract–level socioeconomic deprivation measured via neighborhood deprivation index (NDI) as a standardized score, with Black and White race being ascertained through self-report. Main Outcome and Measures The primary outcome was tissue DNA methylation using genome-wide measurements. The secondary outcome was tissue gene expression. Results Participants included 185 women with breast cancer (110 Black [59.5%], 75 White [40.5%]). Mean (SD) age at surgery was 56.0 (14.1) years. Neighborhood deprivation was higher for Black women than for White women (Mean [SD] NDI, 2.96 [3.03] for Black women and −0.54 [1.91] for White women; difference, −3.50; 95% CI, −4.22 to −2.79; P < .001). In unstratified analysis, 8 hypomethylated CpG sites were identified as associated with the NDI, including sites in 2 tumor suppressor genes, LRIG1 and WWOX. Moreover, expression of the 2 genes inversely correlated with neighborhood deprivation. In the race-stratified analysis, the negative correlation between the LRIG1 gene body CpG site cg26131019 and the NDI remained significant in Black women. A neighborhood deprivation–associated decrease in gene expression was also observed for LRIG1 and WWOX in tumors from Black women. Conclusions and Relevance In this study, high neighborhood deprivation was associated with differences in tissue DNA methylation and gene expression among Black women. These findings suggest that continued investment in public health interventions and policy changes at the neighborhood level may help to remedy biological alterations that could make minoritized populations more susceptible to chronic diseases.