Study identifies risk factors for second colorectal cancer in people with Lynch syndrome

A current study by the German Familial Colorectal Cancer Consortium is looking at the question of which people with Lynch syndrome are at an increased risk of developing a second colorectal cancer. Researchers from the University Hospital Bonn (UKB), the University of Bonn and the University of Leipzig have now published their findings in the journal "Clinical Gastroenterology and Hepatology".

Lynch syndrome (LS), formerly referred to as hereditary non-polyposis colorectal carcinoma (HNPCC), is the most common hereditary cancer predisposition syndrome. It is estimated that around 300,000 people are affected in Germany alone. LS significantly increases the risk of colon cancer and other types of cancer and is responsible for up to around five percent of all colon cancers. It is caused by inherited mutations in DNA mismatch repair genes, which normally correct errors during cell division. When these genes are defective, errors accumulate in the genome, increasing the likelihood of further tumors, including metachronous colorectal cancers, even after successful initial treatment.

Researchers from Bonn and Leipzig therefore investigated risk factors for the occurrence of a second primary colorectal cancer on behalf of the German Familial Colorectal Cancer Consortium. "Our aim is to improve the personalized care of people with Lynch syndrome," says co-senior author Prof. Dr. Jacob Nattermann, Head of the Hepatogastroenterology Section at the UKB's Medical Clinic I (Director: Prof. Christian Strassburg) and member of the Transdisciplinary Research Area (TRA) "Life & Health" at the University of Bonn.

Improved risk assessment for Lynch syndrome

The study draws on data from the central registry of the German Familial Colorectal Cancer Consortium and included 852 individuals with Lynch syndrome who had been diagnosed with a first colorectal cancer. Researchers examined whether variables such as age, sex, tumor location, and genetic subtype influenced the likelihood of developing a second primary colorectal tumor.. "Around one in five of the Lynch syndrome carriers studied developed a second colon cancer over the course of an average of 7.9 years," says lead author Dr. Robert Hüneburg, spokesperson for the German Familial Colorectal Cancer Consortium and senior physician at the Medical Clinic I of the University Hospital Bonn, which is part of the Center for Integrated Oncology (CIO) Bonn. " This study helps refine individualized risk stratification. By systematically evaluating genetic and clinical data, we can better tailor surveillance and counseling for affected individuals."

Increased risk lies in various genes

The study found that the risk of developing a second colorectal cancer depends on which gene is altered in people with Lynch syndrome.People with changes in the MLH1 or MSH2 genes had a higher risk than those with changes in MSH6 or PMS2. This so-called genotype stratification - i.e. risk assessment according to genetic findings - is an important approach for developing individualized prevention strategies.

The analysis is based on one of the largest groups of people with Lynch syndrome examined for this question. The long-term documentation in our registry also makes it possible to map less obvious risk constellations."

Priv.-Doz. Dr. Christoph Engel, co-senior author of the study and head of the Familial Tumor Diseases working group at the Institute of Medical Informatics, Statistics and Epidemiology at Leipzig University

The results of the study underline the benefits of structured registry data for recording the clinical course of hereditary tumor syndromes. They form a basis for the further development of risk-adapted aftercare concepts.