期刊
BREAST CANCER RESEARCH AND TREATMENT
卷 191, 期 3, 页码 653-663出版社
SPRINGER
DOI: 10.1007/s10549-021-06430-1
关键词
Breast cancer; Social epidemiology; DNA methylation; Racial disparity; Mortality
类别
资金
- Winship Cancer Institute of Emory University through the Brenda Nease Breast Cancer Fund
- Glenn Family Breast Center [00067187]
- AVON Foundation for Women [01-2016-087]
- Emory's Integrated Genomics Core shared resource
- Winship Cancer Institute of Emory University
- Applebaum-Peabody Scholarship through the Rollins School of Public Health at Emory University
This study explores the association between neighborhood-level factors and DNA methylation in non-Hispanic Black and White women with breast cancer. It identifies novel associations between neighborhood-level factors and DNA methylation in the breast tumor, and suggests a potential link with all-cause mortality. These findings support the role of neighborhood-level factors in cancer disparities.
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 beta 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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