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Interrogating the Mechanistic Link between Neighborhood Deprivation and Colorectal Cancer Risk through Transcriptomic

Matthew A Devall1,2, Hania M Taha1, Mackenzie Chen1

  • 1Department of Family Medicine, University of Virginia, Charlottesville, Virginia.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
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Summary

Neighborhood deprivation is linked to colorectal cancer (CRC) risk. Metformin may reduce CRC risk by reversing gene expression changes associated with neighborhood deprivation, including MYC.

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Area of Science:

  • Genomics
  • Cancer Biology
  • Health Disparities

Background:

  • Neighborhood deprivation, measured by the Neighborhood Deprivation Index (NDI), is linked to increased colorectal cancer (CRC) risk.
  • The biological pathways connecting NDI to CRC risk are not well understood.

Purpose of the Study:

  • To identify gene expression differences associated with NDI in normal colorectal tissues.
  • To investigate the potential of metformin to reverse these NDI-associated gene expression changes.

Main Methods:

  • RNA sequencing was used to identify differentially expressed genes (DEGs) associated with NDI in normal colorectal biopsies from African Americans (AA) and European Americans (EA).
  • Normal colon organoids derived from AA and EA individuals were treated with metformin, and metformin-associated DEGs were identified.

Main Results:

  • 237 DEGs were associated with NDI across both populations.
  • 82 of these NDI-associated DEGs overlapped with known CRC tumor DEGs, with nine prioritized as therapeutic targets, including MYC.
  • Metformin altered the expression of 28 NDI-associated genes in organoids, with approximately 79% showing opposite expression patterns, including reduced MYC expression.

Conclusions:

  • NDI is associated with distinct transcriptional profiles in the colon that are relevant to CRC.
  • Metformin demonstrated a potential to counteract NDI-associated gene expression changes, suggesting a role in CRC risk reduction.
  • NDI-associated genes represent potential biomarkers and therapeutic targets for CRC in high-risk populations.