How Inflammation Increases Long-Term Colon Cancer Risk

Researchers have identified a molecular mechanism that explains how chronic gut inflammation can increase the risk of colorectal cancer, even after the inflammation has subsided. A study funded in part by the National Institutes of Health (NIH) found that chronic inflammation leaves a heritable epigenetic memory in gut stem cells, which can promote tumor growth long after the initial injury.

The research, conducted by scientists at the Broad Institute of MIT and Harvard and announced on March 25, 2026, utilized mice and organoids derived from injured tissue to track the colon’s response during periods of inflammation and recovery.

The Epigenetic Memory of Inflammation

While an individual’s DNA remains generally stable over time, the epigenome—a collection of chemical annotations to the genome—is dynamic. This flexibility allows cells to adapt to shifting circumstances, such as damaging inflammation, by modulating the expression of genes associated with regeneration.

The study demonstrated that repeated cycles of injury in the gut cause alterations in stem cells. These epigenetic changes were inherited by new cells and persisted for more than 100 days after the colitis had ceased.

These long-lasting alterations increased the activity of a specific group of proteins known as AP-1 transcription factors, which the researchers found promoted the growth of tumors.

The Link Between IBD and Cancer

The findings provide deeper insight into the risks associated with inflammatory bowel disease (IBD), which primarily manifests as ulcerative colitis (UC) and Crohn’s disease (CD). We see established that patients with IBD face an increased risk of various cancers, including colorectal cancer.

The progression from inflammation to carcinogenesis in IBD is driven by an interplay between several factors:

• Long-standing chronic inflammation leading to the accumulation of mutations in epithelial cells.
• The abnormal activation of carcinogenic signaling pathways.
• The influence of the gut microbiota and immune cell interactions.
• Genetic alterations.

The Broad Institute study suggests that the “memory” left in the stem cells provides a biological explanation for why the risk of cancer remains elevated even when the active inflammation is managed.

Potential for Early Intervention

Understanding the specific molecular pathways involved in this process may lead to new clinical applications. By identifying how injury influences cancer risk, researchers hope to develop better methods for early evaluation and therapy.

By spelling out how repeated cycles of injury in the gut may influence colorectal cancer risk, the authors have potentially opened avenues toward much-needed methods of early evaluation and therapy for a condition that is of increasing concern

Anthony Letai, M.D., Ph.D., director of NIH’s National Cancer Institute (NCI)

This research highlights the importance of monitoring long-term gut health in patients with a history of chronic colitis, as the cellular damage persists far beyond the visible resolution of inflammation.