Colorectal cancer has become more common in people under 50 since the mid-1990s, and cases in younger patients often appear more aggressive and resistant to treatment. A new study comparing colorectal tumors from patients ranging in age from 29 to over 90 suggests that differences in the tumors’ cellular makeup and gene activity may help explain why.
The study was published Thursday, October 29, in the journal natural medicine. Researchers found important differences between tumors from younger and older patients, potentially opening new avenues for understanding and treating early-onset colorectal cancer.
Why colorectal cancer in younger people is difficult to treat
“We believe our work is essentially a turning point right now in this field,” Anna Anderson, a professor of neurology at Harvard Medical School and a core faculty member of the Gene Ray Institute of Immunology and Inflammation at Brigham and Women’s Hospital, told Live Science. “Because up until now, there have been more questions than answers.”
Although colorectal cancer has traditionally been associated with older adults, its incidence has risen among people under 50. It is also increasing among children and adolescents. In the United States, colorectal cancer is now a major cause of cancer deaths among people under 50.
Researchers have been investigating not only what is causing the increase, but also why the disease appears to kill more younger patients.
“Clinical data suggest that younger patients’ disease is more aggressive overall,” Anderson said. “These patients are otherwise very healthy, but treatment doesn’t work.”
Differences in tumor composition
To investigate the mystery, Anderson collaborated with Dr. Kimmy Ng, an oncologist at Dana-Farber Cancer Institute, and Dr. Ramnik Xavier, a gastroenterologist at the Broad Institute and Massachusetts General Brigham.
The researchers analyzed RNA from cryopreserved tumor tissue. RNA is a molecular relative of DNA that reflects which genes are active inside a cell. The team studied 189 tumors: 54 from patients younger than 50 and 135 from patients older than 50.
The sample allowed the researchers to compare tumors from younger and older patients overall, as well as to examine gradual changes associated with age. This helped them identify subtle differences, Anderson said.
Tumors from younger patients contained a higher proportion of connective-tissue cells than malignant cancer cells, while the pattern was reversed in older patients. Although a lower proportion of malignant cells might initially seem beneficial, connective tissue inside tumors can release compounds that suppress the immune system. This may help tumors evade immune cells that could otherwise attack and destroy cancer cells.
Connective-tissue cells can also physically obstruct chemotherapy drugs, preventing them from reaching cancer cells. The researchers suggested that this could be one reason tumors in younger patients are more resistant to treatment.
Gene activity may promote cancer spread
Patterns of gene activity in the tumors also suggested that cancer cells from younger patients may have distinct mechanisms for communicating with neighboring cells. These mechanisms could help the cells move through the body more easily than cancer cells in older patients.
Similar gene activity has been associated with more aggressive tumors in other cancers, increasing the likelihood that the disease will spread, or metastasize, Anderson said.
The study also identified a large number of long non-coding RNAs. These RNA strands contain more than 200 building blocks called nucleotides, but they do not provide instructions for making proteins. By contrast, coding RNA travels to protein-making structures inside cells and serves as a blueprint for producing proteins.
Scientists do not yet understand what long non-coding RNA does in the body or specifically within tumors. Anderson and her colleagues hope to determine its role.
The team is already working to manipulate RNA inside cancer cells grown in laboratory dishes. Over time, this research could help explain why colorectal cancer is so aggressive in younger people and identify new ways to target the disease.
“This is a new avenue for studying this disease that we didn’t know existed before,” Anderson said.
This article is for informational purposes only and does not provide medical advice.
Porter, CBM, et al. (2026) Insights into early-onset colorectal cancer from a mononuclear RNA-seq atlas of colorectal cancer across the age continuum. natural medicine.
Source: www.livescience.com