Bowel Tissue Stiffening May Signal Cancer Risk in Younger People
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As colorectal cancer rises rapidly in people under 50, scientists have identified a possible factor beyond genetics: biomechanical stiffening. A new study found that tumors and even normal tissues in younger patients were stiffer and more viscous than in older patients. This physical change may signal cancer cells to activate.
Why Is Cancer Rising in Younger People? When Genetics Is Not Enough
Over the past 30 years, colorectal cancer incidence in people under 50 (early-onset CRC) has increased by 0.5% to 2.4% annually. If current trends continue, an increase of 124% by 2030 is expected.
Most younger patients have no inherited mutation, such as Lynch syndrome. This prompted researchers to investigate the exposome, the totality of environmental exposures, and resulting physical tissue changes.
Researchers biomechanically tested tissue from younger patients, average age 44, and older patients, average age 68. Younger tissue was more fibrotic and mechanically resistant.
Comparison: Younger vs. Older Patients
The study quantified tissue differences between early-onset (EO-CRC) and older-onset (AO-CRC) disease.
*Charts illustrate study trends. In younger patients, shown in red, connective tissue surrounding tumors (stroma) was much stiffer and more organized.
The Mechanism: How Can Stiffness Trigger Cancer?
The study opens a window onto mechanobiology in oncology: the physical environment, as well as chemical signals, can trigger cancer.
Step-by-Step Cancer Development
Diet, obesity or environmental factors initiate chronic bowel inflammation.
Repair attempts produce excess collagen, stiffening tissue like a scar. Younger patients' collagen is more aligned and aggressive in structure.
Cells sense stiffness. The protein YAP (Yes-Associated Protein) responds to the stiff environment by entering the nucleus.
Nuclear YAP instructs the cell to divide and multiply. Even without a genetic mutation, environmental stiffness alone pushes cells toward cancer.
When researchers blocked YAP with verteporfin in the laboratory, cancer cells stopped proliferating despite the stiff substrate, offering hope for future treatment.
Source:
Huning, N. C., et al. (2025). Biomechanical Phenotyping Reveals Unique Mechanobiological Signatures of Early-Onset Colorectal Cancer. Advanced Science.
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Cancer's Physics Matters as Much as Its Genetics
Why is this important? For years, increasing cancer in younger patients prompted genetic testing that often came back clear. This study suggests: Even without inherited genetic findings, physical tissue changes from diet, inactivity and inflammation can initiate cancer.
Environmental exposures, the exposome, effectively harden the bowel wall. Cells sensing a stiff environment perceive a threat and begin uncontrolled proliferation as a defense response.
Colonoscopy might eventually assess bowel-wall stiffness as well as polyps. Increased stiffness could become a biomechanical marker identifying young people at risk long before a tumor develops.