Human genetic diagnostics in oncologic diseases. Importance of tumor risk syndromes for treatment and prevention

It is estimated that 10% of cancer patients carry a congenital genetic alteration associated with a tumor risk syndrome (TRS). Depending on the affected gene and the type of alteration, there is an increased lifetime risk for tumors and possibly other symptoms. Identification of patients with a TRS is of crucial importance for the management, which includes prevention strategies, early detection of disease manifestations, and oncological treatment planning. Due to the hereditary nature of TRS, it is important to consider that not only the affected person but also family members may be at a high risk for tumors, and these persons should therefore be offered carrier testing and, if needed, specialized clinical management. Human genetic institutes serve as the central point of contact for patients and their relatives in this regard. Due to the increasing molecular focus of oncological diagnostics and treatment, which includes comprehensive molecular tests of tumor and normal tissue, TRS are increasingly identified in the context of molecular genetic or molecular pathology tests. The interdisciplinary determination of further clinical management, jointly by all participating specialist disciplines, e.g. within the framework of specialized boards, is of decisive importance to successfully address the challenges of implementing precision oncology. This includes the evaluation of genetic variants, their consequences, and their usability for acute and pre-emptive therapy. Human genetics expertise is crucial for the diagnosis and evaluation of constitutional germline variants in this context and thus contributes to interdisciplinary management of patients and their families.