April 02, 2026
A new study supported by the National Institutes of Health (NIH) has identified a molecular mechanism linking chronic intestinal inflammation to increased colorectal cancer risk. Researchers from the Broad Institute of MIT and Harvard demonstrated that repeated inflammatory injury in the gut induces long-lasting changes in colonic stem cells, promoting tumor development even after inflammation subsides.
Using a mouse model of chronic colitis, scientists tracked tissue damage and recovery, analyzing over 52,000 individual cells. They found that inflammation triggered persistent activation of AP-1 transcription factors—key regulators of cellular stress responses. These changes were epigenetic, altering gene expression without modifying the underlying DNA sequence. Crucially, this “memory” persisted in stem cells for more than 100 days after inflammation ended and was inherited by newly formed cells.
To evaluate the biological impact, researchers introduced tumor-inducing genes into mice that had recovered from colitis. Tumor growth was significantly accelerated in these animals compared to healthy controls, indicating that prior inflammation primes tissue for malignancy.
These findings suggest that chronic inflammation leaves a durable molecular imprint that heightens cancer susceptibility, highlighting new opportunities to identify high-risk individuals and develop therapies aimed at reversing harmful epigenetic programming.
CREDITS: NATIONAL INSTITUTES OF HEALTH