A European study shows that genetic testing of intestinal polyps in patients with many polyps and a negative blood test can reveal additional hereditary risk factors. Researchers at the Radboud University Medical Center and the University Hospital Bonn, in collaboration with teams from Munich and Barcelona, identified mosaic mutations in a relevant proportion of those affected that are only present in intestinal cells. The results were published in the journal Gastroenterology.

Colorectal cancer is one of the most common cancers in the Western world. Hereditary factors play a role in five to ten percent of cases, and the proportion is higher in younger patients. A large number of polyps is considered a strong risk factor: At least ten polyps before the age of 60 or more than 20 before the age of 70 justify genetic clarification by blood analysis. In about a quarter of these patients, a hereditary mutation is found, which entails regular check-ups for those affected and mutation-positive relatives.

In the remaining three-quarters, the blood analysis remains negative, although a hereditary risk is suspected – for example, due to many polyps or familial accumulation. As part of the European Solve-RD consortium, the scientists examined 333 polyps from 180 such patients from all over Europe.

In 80 people with adenomatous polyps, non-hereditary mutations in the APC gene dominated. However, at least 20 percent had an APC mutation mosaic, in which the change is only present in certain body cells, such as the large intestine. Such mosaics are not currently routinely recorded everywhere in Europe. Polyp DNA analysis enables a precise diagnosis here. Siblings of these patients do not have an increased risk, but offspring do. The study also suggests that APC is the only gene in which mosaics play a relevant role in adenomatous polyps without a clear hereditary predisposition.

In about 60 people with serrated polyps, non-hereditary BRAF mutations were found almost universally. Genetically, these polyps resemble an overgrowth of normal intestinal tissue. Whether they will necessarily develop into cancer remains open and requires further investigation.

The analysis not only provides insights into early genetic and epigenetic mechanisms of tumorigenesis in the gastrointestinal tract, but above all creates diagnostic clarity. The identification of APC mosaics relieves many relatives of unnecessary precautions and excludes risks for the majority of children.

In Germany, around 60,000 people are diagnosed with colorectal cancer every year. From the age of 50, a preventive colonoscopy is recommended, which can be repeated after ten years if the findings are normal. Alternatively, a biennial stool test is available. In the case of many polyps, family history or a positive stool test, a colonoscopy is indicated.

The study (DOI: 10.1053/j.gastro.2025.10.011) underlines the added value of polyp DNA analysis as a supplement to blood tests and advocates its integration into standard care.

Original paper:

Mutational Landscape of Colorectal Tumors From Individuals With Unexplained Adenomatous or Serrated Colorectal Polyposis – Gastroenterology

Editor: X-Press Journalistenbüro GbR

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