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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Monday, September 30, 2024
Alexandra Hernandez, MD, MPH, of the University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, and colleagues identified a correlation between neighborhood disadvantage and shorter breast cancer survival through gene expression, DNA methylation, and biologic pathway analysis. Presented during the 2024 American Society of Clinical Oncology (ASCO) Quality Care Symposium (Abstract 48), the results of this study demonstrated a novel regulatory landscape of neighborhood disadvantage on breast cancer.
“These findings can inform interventions such as improved access to healthy nutrition in neighborhood disadvantage/food deserts or targeted stress-reduction interventions based on our survey findings to ultimately reverse aggressive tumor biology and reduce breast cancer disparities by neighborhood disadvantage,” the investigators concluded.
A total of 55 geocoded estrogen receptor–positive, HER2-negative breast cancer samples were obtained from Hispanic White women enrolled in a genomic-epidemiologic cohort study. Neighborhood disadvantage scores from patient-reported surveys were compared with DNA methylation, RNA transcription, and miRNA data, as well as blood concentration levels of DNA methylation cofactors such as vitamin B12 and folate. Correlation analyses were performed to investigate the relationship between DNA methylation/expression pathways and neighborhood deprivation.
High neighborhood disadvantage was observed to correlate with epigenetic deregulation of immune pathways, implying that these pathways may be activated by the reduced systemic ability of methyl donors. A higher tumor infiltration of immune cells consistent with aggressive biology was observed among patients with high neighborhood disadvantage scores via RNA sequencing. Additionally, the downregulation of estrogen response genes suggests that patients with high neighborhood disadvantage scores may develop estrogen-resistant tumors.
Epigenetic changes in calcium signaling genes and cell adhesion, as well as gene expression of E2F targets and the cell cycle’s G2M checkpoint, were associated with higher subjective neighborhood disadvantage scores. Thus, a more proliferative/stemness signature was observed. Furthermore, topologically associated domain analyses identified significant immune, developmental, and signaling pathways when correlating gene expression with DNA methylation.
Disclosure: The study authors reported no conflicts of interest.
2024 ASCO Quality Care Symposium
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