ArticleCancer prevention research (Philadelphia, Pa.)2022
Epigenome-Wide Study Identifies Epigenetic Outliers in Normal Mucosa of Patients with Colorectal Cancer.
Article in Cancer prevention research (Philadelphia, Pa.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 9 citations in OpenAlex.
- Epigenetic fingerprints link early-onset colon and rectal cancer to pesticide exposure.Nature medicine · 2026Article
- Non-invasive epidermis sampling for DNA methylation-based prediction of skin cancer phenotypes.NPJ precision oncology · 2026Article
- Abnormal epigenetic aging of epigenetic outliers in normal colon mucosa from colorectal cancer patients.Scientific reports · 2026Article
- Genome-wide DNA methylation profiles of colorectal tumors in Lynch syndrome and familial adenomatous polyposis.Clinical epigenetics · 2025Article
- Epigenetic age and accelerated aging phenotypes: a tumor biomarker for predicting colorectal cancer.Aging · 2025Article
- Clonal dispersal is associated with tumor heterogeneity and poor prognosis in colorectal cancer.iScience · 2025Article
- Biological Aging in Combination with Lifestyle Factors in the Blood-Based Methylome: A Biomarker for Colorectal Cancer Susceptibility in African American Women.Aging and disease · 2025Article
- Attenuated sex-related DNA methylation differences in cancer highlight the magnitude bias mediating existing disparities.Biology of sex differences · 2024Article
- DNA-methylation variability in normal mucosa: a field cancerization marker in patients with adenomatous polyps.Journal of the National Cancer Institute · 2024Article
- Novel DNA methylation-based epigenetic signatures in colorectal cancer from peripheral blood leukocytes.American journal of cancer research · 2024Article
- Association between gut microbiota and CpG island methylator phenotype in colorectal cancer.Gut microbesArticle
Corrections and comments
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Authors and funding
15 authors at 9 institutions in 1 country.
Funding
Abstract
Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as "Outlier Methylation Phenotype" (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development. PREVENTION RELEVANCE: Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.
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