Epigenome-wide association study of differential DNA-methylation in background mucosa among adults with colorectal adenoma

ABSTRACT: Background: Colorectal adenoma is the primary precursor in colorectal cancer development, partially driven by epigenetic alteration occurring at a very early stage. While aberrant DNA-methylations have been observed in mucosa adjacent to primary tumors, this study aimed to investigate whether such alterations exist in distant background mucosa as global defect rather than local transition, and identify adenoma-related CpG sites which may serve as potential targets for early intervention. Methods: DNA methylation in normal rectal mucosal biopsies from 24 individuals with colorectal adenoma and 20 normal controls were profiled utilizing the Illumina Infinium MethylationEPIC v2.0 BeadChip (935K). Linear regression model was employed to investigate the relationship between adenoma incidence and DNA methylation at each CpG site, adjusted for demographic characteristics. GO and KEGG enrichment analysis were conducted using genes containing CpG sites significantly associated with adenoma. A sensitivity analysis was conducted with individuals who had one or more known risk factors for colorectal adenoma. Results: Twenty-seven CpG sites with aberrant DNA-methylation were significantly correlated with the incidence of adenoma (P<1×10-5, |Δβ|≧0.2). Through GO and KEGG enrichment analysis and lookups in EWAS atlas, a group of CpG sites and genes were identified as potential intervention targets. Conclusions: A group of adenoma-related CpG sites and genes with aberrant DNA-methylation was identified in normal-appearing rectal mucosa. Further extensive validation of the adenoma-related loci as targets for molecular intervention could pave the way for colorectal cancer prevention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE284238 | GEO | 2025/12/31

REPOSITORIES: GEO