Major Study Finds Key Difference in Bowel Cancer Before 50

From newsweek.com

Bowel cancer diagnosed before age 50 may not simply be the same disease appearing earlier in life, according to new research that found key differences in tumour characteristics, genetics and survival among younger patients.

Researchers analysed data from 1,691 Australians whose bowel cancer had spread only to the liver, comparing people diagnosed at age 50 or younger with those diagnosed after 50. Their findings suggest that early-onset bowel cancer has distinct features that could influence how doctors approach treatment.

The study, published in The Medical Journal of Australia, comes as increasing numbers of younger adults are being diagnosed with bowel cancer in Australia, which has one of the world's highest rates of early-onset disease.

Study author Professor Savio George Barreto, from Flinders University, said scientists are still working to understand what is driving the increase in cases among younger adults. He pointed to a theory known as the PELICan hypothesis, which proposes that exposures during key stages of life may contribute to cancer risk.

"We hypothesize that if the cumulative effect of exposures / stressors overwhelms the body’s own protective systems (nutritional, neurohormonal, immune, etc.) at these two critical periods in an individual’s life, it could trigger epigenetic modifications," he told Newsweek.

A stock image shows a gastroenterologist showing a human colon model at table in clinic. | Getty Images

Barreto said factors including smoking, alcohol use, obesity and illicit drug use may play a role, although additional research is needed to prove the hypothesis and determine whether it can help guide prevention and early detection strategies.

Biological Differences Emerging Before Age 50

When the researchers compared younger and older patients, they found several notable differences. Patients diagnosed at 50 or younger were more likely to be women, more likely to have tumours on the left side of the bowel and more likely to carry certain genetic mutations.

Those differences were accompanied by a survival advantage. Younger patients generally lived longer after their cancer had spread to the liver than patients diagnosed later in life.

The findings add to a growing body of evidence suggesting that bowel cancer in younger adults may have a different biological profile from cases diagnosed after age 50.

Barreto said the findings reinforced a theory researchers had suspected for some time. "We were pleasantly surprised that the findings of the study confirmed our long held belief that early-onset cancers possess differences in biology and behaviour compared late-onset disease," he said.

How Genetics Shape Treatment Decisions

Genetics also appeared to play an important role in outcomes.

The researchers found that tumours carrying BRAF or KRAS mutations were linked to poorer outcomes regardless of a patient's age. That pattern was seen in both younger and older groups, highlighting the potential value of genetic testing in understanding how an individual's disease is likely to behave.

The study also identified a potential role for another mutation. "The new finding in this study is the value of NRAS mutations, too, to guide treatment strategies," Barreto said.

Rather than relying on age alone when making treatment decisions, the researchers suggest doctors should pay close attention to the biology of a tumour, its genetic mutations and other disease characteristics.

Such information could help identify patients who may benefit from more individualized treatment approaches.

According to Barreto, genetic information is already becoming increasingly important in clinical decision-making. "The use of BRAF mutations to inform decision making within existing treatment algorithms for our patients is increasing globally," he said. He added that the new findings could also help inform treatment decisions based on tumour location and whether liver metastases appeared at the same time as the primary cancer or developed later.

How Treatment Approaches Differ for Younger Patients

The study also examined how treatment strategies were associated with outcomes.

Patients who had surgery to remove liver tumours followed by drug treatment generally experienced better outcomes than those who received other treatment approaches.

The researchers also observed differences in treatment sequencing between younger and older patients. Barreto said upfront curative surgery, when feasible and associated with minimal morbidity, appeared to provide a greater survival benefit for patients with early-onset disease. By comparison, certain patients in the older cohort, particularly those with right-sided cancers and liver metastases that developed later, appeared to benefit more from receiving chemotherapy first.

However, the researchers emphasized that the findings do not prove the treatment itself caused the improved survival. Because the study was based on real-world clinical data rather than a clinical trial, other factors may have contributed to the difference.

While more research is needed, the results could help inform future investigations into the rising rates of bowel cancer among younger adults.

Supporting Younger Patients Beyond Treatment

Barreto said one priority is understanding how best to support younger survivors, whose needs may differ substantially from those of older patients traditionally served by survivorship programs. He also highlighted the search for biomarkers that could eventually help identify people at higher risk before cancer develops.

"Can we identify epigenetic blood biomarkers of people at risk (if the PELICan hypothesis can be proven)? This will offer the ability to identify individuals at risk early on with the potential for targeted screening in the future," he said.

The researchers say their findings support the idea that early-onset bowel cancer should not automatically be viewed as the same disease affecting older patients. Instead, younger people with the condition appear more likely to have distinct tumour characteristics and genetic patterns, as well as better overall survival in cases where the cancer has spread only to the liver.

Ultimately, understanding those differences could help guide more personalized treatment planning and improve care for patients.

"The main message of the study is that bowel cancer diagnosed before age 50 is not simply the same disease occurring earlier in life," the researchers concluded.

Reference

Savio G. Barreto et al. Early-Onset Colorectal Cancer With Liver-Only Metastases: A Retrospective Cohort Study Integrating Prospectively Collected Real-World Clinical and Molecular Data From an Australian National Database (2009–2024) to Guide Treatment Planning. The Medical Journal of Australia. DOI: 10.5694/mja2.70266

https://www.newsweek.com/major-study-finds-key-difference-in-bowel-cancer-before-50-12394815