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

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.

Figure 1.. DNA Methylation and Gene Expression for the 2 Tumor Suppressor Genes LRIG1 (Locus cg26131019) and WWOX (Locus cg02161209) by Neighborhood Deprivation

In panels A, C, D, and F, the graphs depict a line of fit showing a linear regression with 95% CIs (shaded areas) for 2 continuous variables (x- and y-axes). In panels B and E, the horizonal bar inside the boxes indicates the median, and the lower and upper ends of the boxes are the 25th and 75th percentiles, respectively. The whiskers indicate the minimum and maximum values. P values were derived from the analysis of variance statistical test. Q indicates quartile.

Figure 2.. DNA Methylation and Gene Expression by RNA Sequencing of LRIG1 (Locus cg26131019) by Continuous Neighborhood Deprivation Index, Stratified by Self-Reported Race

In panels A-D, the graphs depict a line of fit showing a linear regression with 95% CIs (shaded areas) for 2 continuous variables (x- and y-axes). In panels E and F, the Kaplan-Meier plots are based on gene chip–derived expression data for LRIG1 from breast tumors (Methods). HR indicates hazard ratio.