Neighborhood characteristics and breast tumor methylation: using epigenomics to explore cancer outcome disparities

Gohar, Jazib; Whitney, L.; Miller‐Kleinhenz, Jasmine M.; Conneely, Karen N.; Krishnamurti, Uma; D’Angelo, Olivia; Gogineni, Keerthi; Torres, Mylin A.; Gabram-Mendola, Sheryl; McCullough, Lauren E.

doi:10.1007/s10549-021-06430-1

Cited by 12 publications

(13 citation statements)

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“…Empirical studies designed explicitly to test whether stress and genomic inflammatory markers mediate associations between racism and breast cancer are lacking. However, one study has reported differential breast tumor methylation of numerous genes by neighborhood socioeconomic factors, with at least 1 such gene also correlating with mortality following a breast cancer diagnosis . Future studies of HOLC residence and cancer outcomes should strive to collect such additional measures as interpersonal discrimination, individual socioeconomic status, stress, and markers of inflammation to test these hypotheses.…”

Section: Discussionmentioning

confidence: 99%

Association Between Residence in Historically Redlined Districts Indicative of Structural Racism and Racial and Ethnic Disparities in Breast Cancer Outcomes

Plascak

Beyer

et al. 2022

JAMA Netw Open

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Key Points Question Is historical mortgage lending discrimination (1930s redlining) associated with recent breast cancer outcomes differently by race and ethnicity? Findings In this cohort study of 14 964 breast cancer cases, we found evidence that residence at diagnosis in areas historically graded “best” (vs residence in redlined areas) was associated with lower odds of late-stage diagnosis, lower odds of high tumor grade, lower odds of triple-negative subtype, and lower hazard of breast cancer–specific death, but only among non-Latina White women. Meaning These findings suggest that historical structural racism may be associated with beneficial cancer outcomes among privileged racial and ethnic groups.

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Section: Discussionmentioning

confidence: 99%

Association Between Residence in Historically Redlined Districts Indicative of Structural Racism and Racial and Ethnic Disparities in Breast Cancer Outcomes

Plascak

Beyer

et al. 2022

JAMA Netw Open

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“…This is a promising line of inquiry: further research is needed on the possible epigenetic changes brought about by past and present neighborhood deprivation and which of these changes may lead to worse breast cancer prognoses. 72 Understanding the interplay among race, SES, area-level deprivation during the life course, and breast cancer outcomes may lead to better intervention strategies for narrowing the disparity gap.…”

Section: Discussionmentioning

confidence: 99%

“…However, our data do not contain historic living conditions for patients, but only their last known address; we therefore can make no claims about this, for some Black women in our study cohort may have lived in less-deprived areas all their lives. This is a promising line of inquiry: further research is needed on the possible epigenetic changes brought about by past and present neighborhood deprivation and which of these changes may lead to worse breast cancer prognoses . Understanding the interplay among race, SES, area-level deprivation during the life course, and breast cancer outcomes may lead to better intervention strategies for narrowing the disparity gap.…”

Section: Discussionmentioning

confidence: 99%

Association of Race and Area Deprivation With Breast Cancer Survival Among Black and White Women in the State of Georgia

et al. 2022

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ImportanceIncreasing evidence suggests that low socioeconomic status and geographic residence in disadvantaged neighborhoods contribute to disparities in breast cancer outcomes. However, little epidemiological research has sought to better understand these disparities within the context of location.ObjectiveTo examine the association between neighborhood deprivation and racial disparities in mortality among Black and White patients with breast cancer in the state of Georgia.Design, Setting, and ParticipantsThis population-based cohort study collected demographic and geographic data from patients diagnosed with breast cancer between January 1, 2004, and February 11, 2020, in 3 large health care systems in Georgia. A total of 19 580 patients with breast cancer were included: 12 976 from Piedmont Healthcare, 2285 from Grady Health System, and 4319 from Emory Healthcare. Data were analyzed from October 2, 2020, to August 11, 2022.ExposuresArea deprivation index (ADI) scores were assigned to each patient based on their residential census block group. The ADI was categorized into quartile groups, and associations between ADI and race and ADI × race interaction were examined.Main Outcomes and MeasuresCox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% CIs associating ADI with overall mortality by race. Kaplan-Meier curves were used to visualize mortality stratified across racial and ADI groups.ResultsOf the 19 580 patients included in the analysis (mean [SD] age at diagnosis, 58.8 [13.2] years), 3777 (19.3%) died during the course of the study. Area deprivation index contributed differently to breast cancer outcomes for Black and White women. In multivariable-adjusted models, living in a neighborhood with a greater ADI (more deprivation) was associated with increased mortality for White patients with breast cancer; compared with the ADI quartile of less than 25 (least deprived), increased mortality HRs were found in quartiles of 25 to 49 (1.22 [95% CI, 1.07-1.39]), 50 to 74 (1.32 [95% CI, 1.13-1.53]), and 75 or greater (1.33 [95% CI, 1.07-1.65]). However, an increase in the ADI quartile group was not associated with changes in mortality for Black patients with breast cancer (quartile 25 to 49: HR, 0.81 [95% CI, 0.61-1.07]; quartile 50 to 74: HR, 0.91 [95% CI, 0.70-1.18]; and quartile ≥75: HR, 1.05 [95% CI, 0.70-1.36]). In neighborhoods with an ADI of 75 or greater, no racial disparity was observed in mortality (HR, 1.11 [95% CI, 0.92-1.36]).Conclusions and RelevanceBlack women with breast cancer had higher mortality than White women in Georgia, but this disparity was not explained by ADI: among Black patients, low ADI was not associated with lower mortality. This lack of association warrants further investigation to inform community-level approaches that may mitigate the existing disparities in breast cancer outcomes in Georgia.

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“…Few studies have sought to uncover the biological mechanisms that mediate the association between neighborhood environment and disease . One study investigated the association of contemporary redlining with DNA methylation in breast tumors and found redlining-associated methylation of CpG sites in genes previously linked to breast carcinogenesis .…”

Section: Introductionmentioning

confidence: 99%

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

Jenkins,

Rossi,

Pichardo

et al. 2023

JAMA Netw Open

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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 &lt; .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.

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Neighborhood characteristics and breast tumor methylation: using epigenomics to explore cancer outcome disparities

Cited by 12 publications

References 50 publications

Association Between Residence in Historically Redlined Districts Indicative of Structural Racism and Racial and Ethnic Disparities in Breast Cancer Outcomes

Association Between Residence in Historically Redlined Districts Indicative of Structural Racism and Racial and Ethnic Disparities in Breast Cancer Outcomes

Association of Race and Area Deprivation With Breast Cancer Survival Among Black and White Women in the State of Georgia

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

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