Scientists from UT Southwestern Medical Center and the University of Texas at Dallas have found a possible reason why more younger adults are developing colorectal cancer (CRC).
Their new study shows that when the colon becomes stiff due to long-term inflammation, it may increase the risk of early-onset CRC. This finding could help improve how we prevent and treat this serious disease.
Colorectal cancer usually affects people over 50. These cases are known as average-onset CRC. In recent years, these cases have gone down, mostly due to better screening and lifestyle changes. But CRC in people under 50—called early-onset CRC—has been rising quickly.
Since 2020, about 12% of all CRC cases in the U.S. have been diagnosed in younger adults. Scientists haven’t fully understood why this is happening.
The new study, published in the journal Advanced Science, looked at how chronic inflammation might play a role. Inflammation can cause tissue damage and scarring, which makes the colon stiffer over time.
This stiffening has already been shown to help certain cancers grow, like breast and pancreatic cancer. Researchers wanted to find out if the same process could be happening in the colon.
To test this, the team studied tissue samples from people who had colorectal tumors removed during surgery. There were 14 samples from patients with early-onset CRC and 19 from those with average-onset CRC. The scientists tested not just the tumors, but also the surrounding non-cancerous tissue.
They found that both the tumors and the nearby normal tissue were stiffer in younger patients. This suggests that the increased stiffness may have happened before the cancer even started, possibly contributing to its development.
The researchers then looked at collagen, a protein that plays a big role in tissue structure. They found that the collagen in early-onset CRC samples was thicker, more tightly packed, and more mature compared to the average-onset samples. This supports the idea that scarring from inflammation was making the colon stiffer.
To understand how this stiffness might lead to cancer, the team looked at which genes were active in the tissues. They found that the early-onset CRC samples had higher activity in genes related to collagen production, inflammation, and blood vessel growth.
They also saw signs of increased mechanotransduction—a process where cells sense and respond to the stiffness of their surroundings.
When they grew cancer cells on soft and stiff surfaces in the lab, the results were clear: cells on stiffer surfaces grew faster and formed larger clumps. The same was true when they used 3D models called organoids made from cancer cells.
These results suggest that when the colon becomes too stiff, it may send signals to nearby cells that encourage them to grow uncontrollably. This might be one way early-onset CRC begins.
Dr. Emina Huang, who co-led the study, said this discovery could help doctors find new ways to prevent and treat early-onset CRC. In the future, tests that measure colon stiffness could help identify people who are at higher risk, similar to how colonoscopies are used to spot CRC in older adults.
There is also hope that new treatments could target the pathways that allow cells to respond to stiffness, possibly stopping cancer before it starts.
This study represents a major step toward understanding the rise in early-onset CRC and opens the door to better diagnostics and therapies.
If you care about cancer, please read studies that artificial sweeteners are linked to higher cancer risk, and how drinking milk affects risks of heart disease and cancer.
For more health information, please see recent studies about the best time to take vitamins to prevent heart disease, and results showing vitamin D supplements strongly reduces cancer death.
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