Chronic inflammation can increase cancer risk, and new research reveals important details about how it happens in the gut and points to better ways to identify and reduce risk.
Scientists at the Broad Institute and Harvard University have shown in mice that after colitis or chronic enteritis, seemingly healed intestinal tissue retains memories of early inflammation through molecular “scars” that may make it easier for cancer to later take hold. These memories are encoded as changes in the epigenome that are passed from cell to cell through generations of cell division and can have long-term effects on gene activity and later promote tumor growth.
Appeared in natureThis study suggests a two-step process that occurs over time in which genomic changes (epigenetic changes and cancer mutations) can accelerate tumor growth. We also demonstrate how these cancer-promoting factors can potentially be identified and potentially intervened with new biomarkers and treatments..
“This discovery is a great example of how our experiences and exposures influence our future health,” said study lead author Jason Buenrostro, a Broad core member and professor in the Department of Stem Cell and Regenerative Biology at Harvard University, leader of the Broad’s Adversity Biology Project, and co-investigator of the cancer grand challenge team PROSPECT. “We showed that epigenetic changes are the missing piece in how inflammation causes cancer.”
epigenome scars
Colorectal cancer has increased dramatically among young people in recent decades, indicating that changes in diet, lifestyle, or exposure to toxins may be increasing risk, rather than changes in genetic mutations, which can take thousands of years to develop.
“These factors are temporary. What you eat in adolescence is not what you eat now, but it can influence your lifelong cancer risk,” said study lead author Surya Nagaraja, a postdoctoral fellow in Buenrostro’s lab, a pathology fellow at Massachusetts General Hospital, and a member of Team PROSPECT.
In the new study, researchers focused on chronic inflammation, one of the biggest risk factors for cancer across tissues. Researchers induced inflammation in the intestines in animal models and observed changes in cells within the colon.
Researchers have developed a way to measure several things at once in individual cells. epigenomic state, or which parts of the genome are accessible and genes in those regions can be turned on or off. and the history of cloning that reveals the family tree of cells.
Even after the inflammation subsided and the tissue appeared to be healed, the researchers observed that some cells retained long-term epigenetic memory of the exposure, allowing certain DNA sites to remain open and accessible even after gene expression returned to normal.
Then, when the scientists introduced cancer-promoting mutations, tissues with epigenetic memory developed larger tumors and grew faster than tissues without inflammation. The tissue did so by activating a set of genes that contribute to cancer growth, and through inflammatory memory became more accessible and therefore more easily regulated.
The study concludes that this epigenetic memory is the first in a “one-two punch” that can last a lifetime, allowing subsequent mutations to initiate tumor growth. The researchers found that stem cells with the strongest epigenetic memory passed on their changes to their “daughter” cells, creating an entire family of cancer-ready cells.
In the epigenome, we found that these long-lived and powerful effects were just waiting for an opportunity to influence gene expression, and we needed to look at the epigenetic layer to confirm these effects. ”
Jason Buenrostro, Broad Core Member, Professor, Department of Stem Cell and Regenerative Biology, Harvard University
He added that the group’s findings could lead to a rethinking of how cancer develops. “We all walk around with cancer-related mutations, but not all of us have cancer. It’s not just the genetic mutations that matter. The type of cell and the experiences it has determines the outcome of the disease.”
Researchers are studying whether these molecular scars can be found in human stool samples to identify at-risk individuals. These new clues may also open the door to future treatments that target and modify the underlying mechanisms.
“Team PROSPECT is working to uncover important insights into the rising global incidence of colorectal cancer in young adults. These latest findings, if validated in humans, suggest that chronic inflammation early in life can influence the risk of colon cancer decades later. Importantly, this discovery will help understand who is most at risk and inform new approaches to prevent or stop the disease at an earlier stage. “This is a powerful example of the kind of breakthroughs Grand Challenges are designed to achieve.” David Scott, Cancer Grand Challenges Director.
The study was part of PROSPECT, an international research team led by Andy Zhang and Ying Chao investigating the rise in colorectal cancer in young adults worldwide. PROSPECT is part of Cancer Grand Challenges, a global research initiative that identifies the toughest challenges in cancer research and enables multidisciplinary teams from around the world to tackle them. Through Cancer Grand Challenges, team PROSPECT receives funding from Cancer Research UK, the US National Cancer Institute, Cancer Research UK Gut Babe Fund and the French National Cancer Institute.
sauce:
Extensive research labs at MIT and Harvard University
Reference magazines:
Nagaraja, S. others. (2026). Epigenetic memory of colitis promotes tumor growth. nature. DOI: 10.1038/s41586-026-10258-4. https://www.nature.com/articles/s41586-026-10258-4
