The Role of DNA Methylation in Gastrointestinal Disease: An Expanded Review of Malignant and Nonmalignant Gastrointestinal Diseases

Esophageal, colorectal, pancreatic, hepatocellular, and gastric cancer together impact millions of patients worldwide each year, with high overall mortality rates and are increasing in incidence. Additionally, premalignant gastrointestinal diseases such as Barrett's esophagus and inflammatory bowel disease are also increasing in incidence. However, involvement of aberrant DNA methylation in these diseases is incompletely understood, especially given recent research advancements in this field. Here, we review knowledge of this epigenetic mechanism in gastrointestinal preneoplasia and neoplasia, considering mechanisms of action, genetic and environmental factors, and CpG island methylator phenotype. We also highlight developments in translational research, focusing on genomic-wide database data, methylation-based biomarkers and diagnostic tests, machine learning, and therapeutic epigenetic strategies.