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

Abstract

ImportanceThe biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood.ObjectiveTo determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer.Design, Setting, and ParticipantsThis 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.ExposureYear 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 MeasuresThe primary outcome was tissue DNA methylation using genome-wide measurements. The secondary outcome was tissue gene expression.ResultsParticipants 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 RelevanceIn 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.