Chronic inflammation has long been implicated in cancer risk. New evidence in mice indicates that even after colitis appears to resolve, gut tissues can carry durable epigenetic “scars” that later accelerate tumor growth. The work, published in Nature in 2026 by researchers at Harvard University and the Broad Institute, outlines a two-step process in which persistent, inflammation-encoded epigenetic changes set the stage for later oncogenic mutations to drive colorectal cancer more aggressively.
Colitis can leave the colon “primed” for cancer in a two-step process
- Initial event: chronic intestinal inflammation (colitis) induces long-lasting changes in the epigenome of certain colon cells, even after tissue appears healed.
- Persistence: epigenetic “memory” is passed through stem-cell lineages, maintaining open chromatin at specific DNA sites despite normalized gene expression.
- Second hit: when a cancer-promoting mutation arises later, cells with epigenetic memory activate oncogenic programs more readily, producing larger and faster-growing tumors in mouse models.
- Translational signal: researchers are exploring whether these molecular scars can be detected noninvasively in human stool to help identify people at higher risk.
“This finding is a great example of how our experiences and exposures affect our future health,” said Jason Buenrostro, who led the study team. “We’ve shown that epigenetic changes are the missing piece in how inflammation leads to cancer.”
“In the epigenome, we see this long-lived, robust effect, just waiting for its chance to affect gene expression, and we needed to look at the epigenetic layer in order to see these effects.”
Buenrostro added: “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.”
What the mouse data show about mechanism and durability
| Study element | Key detail |
|---|---|
| Biological model | Mouse colitis model followed by introduction of a cancer-promoting mutation |
| Cell-level readouts | Single-cell profiling of gene expression, chromatin accessibility (epigenome), and clonal history |
| Lasting effect | Open chromatin sites persist in some cells after inflammation resolves, encoding a “memory” |
| Tumor behavior | Cells with strong epigenetic memory formed larger, faster-growing tumors after the oncogenic hit |
| Heritability | Stem cells transmitted epigenetic memory to daughter cells, creating lineages primed for tumorigenesis |
| Potential biomarker | Feasibility of identifying inflammation-linked epigenetic features in stool under exploration |
Population trends and system-level relevance
Colorectal cancer has been rising among younger adults in multiple countries, a shift more consistent with environmental exposures and lifestyle patterns than with changes in inherited genetics. The new findings intersect with those trends by highlighting how inflammatory exposures earlier in life could leave persistent molecular imprints that matter decades later, especially for people living with chronic inflammatory bowel diseases such as ulcerative colitis and Crohn’s colitis.
- Population impact: early-onset colorectal cancer has increased over recent decades, altering screening and awareness strategies in health systems.
- Risk architecture: chronic intestinal inflammation (ulcerative colitis, Crohn’s colitis) remains an established risk factor for colorectal cancer, alongside family history, certain hereditary syndromes, tobacco exposure, heavy alcohol use, obesity, and physical inactivity.
- Health-service planning: if stool-based epigenetic markers prove reliable, they could complement current tools by flagging individuals who merit closer surveillance, with implications for referral pathways, colonoscopy demand, and payer coverage standards.
Policy snapshot: how current U.S. screening guidance fits
The emerging biology lands in a policy landscape that already treats colorectal cancer screening as a core population-health obligation. In the United States, federal preventive-services guidance is a key reference point for clinicians, insurers, and state programs.
| Authority | Age range (average risk) | Modality notes |
|---|---|---|
| U.S. Preventive Services Task Force | 45-75 years (routine); 76-85 years (selective, individualized) | Multiple options are endorsed in guideline frameworks (for example, stool-based tests and colonoscopy), with intervals determined by test type and results. People with inflammatory bowel disease or other high-risk conditions are typically managed under separate, more intensive surveillance protocols. |
- Policy levers: validation of epigenetic stool markers could inform future updates to guideline frameworks if clinical utility is demonstrated and if they outperform or complement existing stool-based tests.
- Capacity considerations: any shift toward risk-stratified screening requires workforce planning for endoscopy, primary care triage, and pathology services, as well as attention to regional bottlenecks.
- Payment and coverage: payers typically require evidence of analytical validity, clinical validity, and clinical utility before adopting new diagnostics at scale, and preventive-services mandates often hinge on whether a test is incorporated into national recommendations.
From bench to biomarker: regulatory and implementation checkpoints
If inflammation-linked epigenetic signatures in stool move toward clinical use, they will enter a tightly regulated diagnostics space overseen in the United States by the Food and Drug Administration and by payers who decide whether and how to reimburse new tests.
- Analytical performance: reproducibility across laboratories, lot-to-lot consistency, and defined cutoffs for positivity are prerequisites for clinical deployment.
- Clinical validity: large, diverse cohorts are needed to test whether inflammation-linked epigenetic features reliably predict incident colorectal neoplasia beyond current risk tools.
- Regulatory pathway: stool-based epigenetic assays intended for diagnosis or screening generally require in vitro diagnostic clearance or approval under the governing medical device framework set out in the U.S. medical device regulations, with rigorous evidence packages.
- Integration: interoperability with electronic health records, standardized reporting, and clear follow-up pathways will be essential to avoid overuse, duplicate testing, or missed follow-up.
Equity lens: ensuring benefits reach high-risk and underserved groups
Because inflammatory bowel disease and colorectal cancer burdens fall unevenly across populations, any epigenetic biomarker strategy risks widening gaps if equity is not designed in from the outset.
- Access: communities with limited endoscopy availability could benefit from accurate noninvasive triage tools if paired with guaranteed pathways to diagnostic colonoscopy.
- Representation: biomarker development must include participants across ages, races and ethnicities, geographies, and IBD subtypes to ensure performance generalizes.
- Affordability: out-of-pocket costs and prior-authorization policies can deter uptake; value-based coverage decisions will hinge on real-world effectiveness and budget impact for public and private payers.
Limitations and what researchers aim to clarify next
For policymakers and clinicians, the central caveat is that this is still early-stage science. The mechanistic signal in mice is strong, but translation to human risk prediction remains unproven.
- Species and setting: findings are from mouse models; human validation is necessary before clinical implications are drawn or screening policies are reconsidered.
- Causality chain: while epigenetic memory plus mutation accelerates tumors in mice, researchers must test whether the same signatures forecast risk in humans prospectively and add value on top of existing clinical risk factors.
- Feasibility: detecting subtle chromatin-accessibility signatures in stool at population scale requires robust, cost-effective assays and careful thresholding to balance sensitivity and specificity.
“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. Importantly, the discovery could help us understand who is most at risk and inform new approaches to prevent or intercept the disease at an earlier stage. It is a powerful example of the kinds of breakthroughs Cancer Grand Challenges was designed to achieve,” said David Scott, who leads the Cancer Grand Challenges program.
Key takeaways for public health planning
- Chronic gut inflammation may leave durable epigenetic marks that predispose to malignancy years later, reframing the “window” for cancer prevention and suggesting that control of inflammatory bowel disease could have long-tail cancer benefits.
- Risk-stratified screening built on validated biomarkers could target resources more efficiently, but only with strong evidence, clear regulatory pathways, and equitable implementation across health systems.
- Health systems will need multidisciplinary coordination-gastroenterology, pathology, primary care, data science, and payers-to responsibly translate epigenetic insights into practice and to decide when they justify changes to guidelines, benefit design, and capacity planning.