Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
Interrogating the Mechanistic Link between Neighborhood Deprivation and Colorectal Cancer Risk through Transcriptomic Analysis of Normal Colorectal Biopsies.
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Devall Matthew A, Taha Hania M, Chen Mackenzie, Eaton Stephen D, Sun Xiangqing, Venkatesh Samyukta, Ramirez Alexa, Habib Fatima Z, Ali Mourad W, Cooper Gregory S, Willis Joseph, Hu Gaizun, Ebrahim Seham, Schmit Stephanie L, Peters Ulrike, Powell Steven M, Yoshida Cynthia, Li Li
Аннотация
BACKGROUND: Greater neighborhood deprivation, as defined by the neighborhood deprivation index (NDI), has been associated with increased colorectal cancer risk. However, the biological mechanisms underlying this association remain unclear.
METHODS: Normal colorectal biopsies (matched right and left colon and rectum) from African American [AA (n = 34)] and European American [EA (n = 23)] adults undergoing colonoscopy were collected for a cross-sectional study in Cleveland, Ohio. NDI-associated differentially expressed genes (DEG) were identified from RNA sequencing using limma. Normal colon organoid lines were derived from biopsies of AA (n = 4) and EA (n = 6) individuals in Charlottesville, Virginia, treated daily with metformin for 72 hours, and metformin-DEGs were identified in limma.
RESULTS: A total of 237 DEGs were found to be commonly associated with NDI in AA and EA populations across individual-matched biopsy triplets (right and left colon and rectum). Of the 237 NDI-associated DEGs, 82 overlapped with colorectal cancer tumor DEGs from a publicly available dataset (P = 2.21E-05), and 9 were prioritized as therapeutic targets, including MYC overexpression [Benjamini-Hochberg (BH) = 2.48E-12]. Metformin exposure in colon organoids also altered the expression of 28 of these genes, with ∼79% showing the opposite direction, including reduced MYC expression (BH = 0.095).
CONCLUSIONS: NDI is associated with colorectal cancer-related transcriptional differences. The observed reversal of gene expression by metformin, including at MYC, suggests a potential role for metformin in reducing colorectal cancer risk by modifying NDI-high related gene expression.
IMPACT: NDI-associated colorectal cancer risk genes provide a novel opportunity for future biomarkers or early therapeutic targets in at-risk populations.
METHODS: Normal colorectal biopsies (matched right and left colon and rectum) from African American [AA (n = 34)] and European American [EA (n = 23)] adults undergoing colonoscopy were collected for a cross-sectional study in Cleveland, Ohio. NDI-associated differentially expressed genes (DEG) were identified from RNA sequencing using limma. Normal colon organoid lines were derived from biopsies of AA (n = 4) and EA (n = 6) individuals in Charlottesville, Virginia, treated daily with metformin for 72 hours, and metformin-DEGs were identified in limma.
RESULTS: A total of 237 DEGs were found to be commonly associated with NDI in AA and EA populations across individual-matched biopsy triplets (right and left colon and rectum). Of the 237 NDI-associated DEGs, 82 overlapped with colorectal cancer tumor DEGs from a publicly available dataset (P = 2.21E-05), and 9 were prioritized as therapeutic targets, including MYC overexpression [Benjamini-Hochberg (BH) = 2.48E-12]. Metformin exposure in colon organoids also altered the expression of 28 of these genes, with ∼79% showing the opposite direction, including reduced MYC expression (BH = 0.095).
CONCLUSIONS: NDI is associated with colorectal cancer-related transcriptional differences. The observed reversal of gene expression by metformin, including at MYC, suggests a potential role for metformin in reducing colorectal cancer risk by modifying NDI-high related gene expression.
IMPACT: NDI-associated colorectal cancer risk genes provide a novel opportunity for future biomarkers or early therapeutic targets in at-risk populations.