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

  • Epidemiology
  • Published:
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Abstract

Background

Social exposures may drive epigenetic alterations that affect racial disparities in breast cancer outcomes. This study examined the association between neighborhood-level factors and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer.

Methods

Genome-wide DNA methylation was measured using the EPIC array in the tumor tissue of 96 women. Linear regression models were used to examine the association between nine neighborhood-level factors and methylation, regressing β values for each cytosine-phosphate guanine dinucleotide (CpG) site on neighborhood-level factors while adjusting for covariates. Neighborhood data were obtained from the Opportunity Atlas. We used a false discovery rate (FDR) threshold < 0.05, and for CpGs below this threshold, we examined interactions with race. We employed multivariable Cox proportional-hazards models to estimate whether aberrant methylation was associated with all-cause mortality.

Results

26 of the CpG sites were associated with job density or college education (FDR < 0.05). Further exploration of these 26 CpG sites revealed no interactions by race, but a single probe in TMEM204 was associated with all-cause mortality.

Conclusion

We identified novel associations between neighborhood-level factors and the breast tumor DNA methylome. Our data are the first to show that dysregulation in neighborhood associated CpG sites may be associated with all-cause mortality. Neighborhood-level factors may contribute to differential tumor methylation in genes related to tumor progression and metastasis. This contributes to the increasing body of evidence that area-level factors (such as neighborhood characteristics) may play an important role in cancer disparities through modulation of the breast tumor epigenome.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to IRB protocol but are available from the corresponding author on reasonable request to study PI (lauren.mccullough@emory.edu).

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Acknowledgements

This work was funded by Developmental Funds from the Winship Cancer Institute of Emory University through the Brenda Nease Breast Cancer Fund and the Glenn Family Breast Center (PI: LEM, Grant No. 00067187), as well as the AVON Foundation for Women (PI: SGM, Grant No. 01-2016-087). The research was supported, in part, by Emory's Integrated Genomics Core shared resource, a core supported by the Winship Cancer Institute of Emory University. JG was supported in part by the Applebaum-Peabody Scholarship through the Rollins School of Public Health at Emory University. Fresh tumor specimens from breast cancer patients were obtained from the Breast Satellite Tissue Bank, Winship Cancer Institute, Emory University, Atlanta, GA, USA

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Authors and Affiliations

  1. Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, 30322, USA

    Jazib Gohar, Jasmine Miller-Kleinhenz & Lauren E. McCullough

  2. Department of Global Health, Emory University Rollins School of Public Health, Atlanta, GA, 30322, USA

    Whitney L. Do

  3. Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Karen Conneely

  4. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Uma Krishnamurti

  5. Department of Surgery, Jackson Memorial Hospital/University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Olivia D’Angelo

  6. Department of Medical Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Keerthi Gogineni

  7. Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Mylin Torres

  8. Department of Surgery, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Sheryl Gabram-Mendola

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Contributions

LEM conceived the research and designed the study. LEM, SGM, and KG secured funding for the research. OD, MT, and LEM, curated clinical data for the research. UK and LEM obtained and processed specimens. LEM, WD, JG, and KC drafted the analytic plan and supervised all the work. JG and WD performed the statistical analysis. LEM, JG, WD, and JMK aided in data interpretation. LEM, JG, WD, and JMK drafted the manuscript. All authors contributed to the development of the manuscript.

Corresponding author

Correspondence to Lauren E. McCullough.

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SGM Board Member TurningPoint Breast Cancer Rehabilitation, a 501c3 organization in Atlanta.

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Gohar, J., Do, W.L., Miller-Kleinhenz, J. et al. Neighborhood characteristics and breast tumor methylation: using epigenomics to explore cancer outcome disparities. Breast Cancer Res Treat 191, 653–663 (2022). https://doi.org/10.1007/s10549-021-06430-1

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