Scientists from the Broad Institute and Harvard University reported on Mar. 25 that chronic intestinal inflammation can leave lasting molecular changes in gut tissue, increasing the risk of cancer later in life. The study, published in Nature, used a mouse model to show that even after apparent healing from colitis, cells in the gut retain an "epigenetic memory" of inflammation, making them more susceptible to tumor growth if they acquire certain mutations.
This research matters because colorectal cancer rates have risen sharply among younger people over recent decades. According to the scientists, these increases are likely due to shifts in diet, lifestyle, or exposure to toxins rather than inherited genetic changes.
The researchers developed a method for measuring gene expression patterns and epigenomic states at the single-cell level. They found that after inflammation subsided and tissues appeared healed, some cells kept DNA sites open and accessible—a sign of epigenetic memory—even as normal gene activity resumed. When a cancer-promoting mutation was introduced into these tissues with prior inflammation history, tumors grew larger and faster compared to those without such history.
Senior author Jason Buenrostro said: "This finding is a great example of how our experiences and exposures affect our future health... We've shown that epigenetic changes are the missing piece in how inflammation leads to cancer." First author Surya Nagaraja added: "These factors are transient - your diet in adolescence is not your diet now, but it can affect your cancer risk over a lifetime." Buenrostro also commented: "We all walk around with cancer-related mutations, but we don't all have cancer. It's not just the genetic mutation that matters - the cell type and the experiences that cell has will determine disease outcomes."
The team is investigating whether these molecular scars can be detected in human stool samples as biomarkers for increased risk. This could help identify individuals most at risk for colorectal cancer and guide new preventive strategies.
David Scott, Director of Cancer Grand Challenges, said: "Team PROSPECT is working to uncover important insights into the rising global incidence of colorectal cancer in younger adults... If validated in humans, these latest findings suggest that chronic inflammation earlier in life could affect a person's risk of colon cancer decades later... It is a powerful example of the kinds of breakthroughs Cancer Grand Challenges was designed to achieve." Team PROSPECT's work is funded by several organizations including Cancer Research UK and the US National Cancer Institute.
