The genetic confirmation of a suspected diagnosis of hereditary colorectal cancer is of great importance for the medical care of affected families. However, many of the variants identified in the known genes cannot yet be reliably classified in terms of their causal role in tumor formation. Under the leadership of the University Hospital Bonn (UKB) and the University of Bonn, an international team of researchers has reassessed the medical relevance of a significant number of unclear variants and thus significantly reduced their number.
The results of the study have now been published in The American Journal of Human Genetics. Families with hereditary tumor diseases have a high risk of developing certain cancers such as colon cancer or breast cancer. For many common hereditary tumor syndromes, there are now very effective, intensive and early cancer screening programs and other preventive measures.
Timely detection and reliable diagnosis of a hereditary predisposition is therefore extremely important for the families affected. Due to increasingly comprehensive genetic testing, however, more and more genetic variants are being found in the responsible genes whose causal significance for the development of tumors is still unclear. These are referred to as variants of uncertain significance (VUS).
As a result, more than 50% of the variants for some genes listed in public international databases (in particular ClinVar) are now VUS. "These cannot be used for diagnosis or for testin.