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Germany’s Genetic Diagnostics Act (Genetikdiagnostikgesetz, GenDG) defines in paragraph 3 No 4 as follows: in the sense of this law (verbatim, in translation), “genetic attributes are inherited genetic information, or genetic information acquired during fertilization or in the time leading up to the birth, which originate in the human being.” In the rationale for the law, the following explanation is given: “Somatic genetic changes—that is, changes that occur in only a proportion of the body’s cells and as a rule not in the gametes, are not captured by Germany’s Genetic Diagnostics Act because the regulatory requirement of the act assumes the particularity of genetic data. These have a predictive value beyond the tested individual, and their validity is not time limited (that is, they are valid for an entire lifespan). These characteristics do not apply to somatic genetic changes.”
Microsatellite instability (MSI) or loss of mismatch repair protein (MMR) expression are found only in the tumor in HNPCC. Once this has been surgically removed, MSI and MMR loss are gone from the patient’s body. The Genetic Diagnostics Act therefore does not apply.
Germany’s HNPCC consortium found a pathogenic germline mutation in an MMR gene in 46% of all families that met the Amsterdam I criteria and in 54% of families that met the Amsterdam II criteria. When MSI or MMR loss were also included, 69% and 78% of families, respectively, had a pathogenic mutation in an MMR gene. The molecular pathological changes are a necessary condition, but not an adequate one for detecting a clinically relevant risk increase for a germline mutation in an MMR gene. Familial findings are of far greater relevance.
In our opinion, investigating tumors for MSI or MMR expression is not subject to the genetic diagnostics law. Patients are therefore not required to give written consent according to Germany’s Genetic Diagnostics Act.
Dr. med. Verena Steinke, Prof. Dr. med. Peter Propping
Institut für Humangenetik,
Dr. med. Christoph Engel
Institut für Medizinische Informatik,
Statistik und Epidemiologie,
Prof. Dr. med. Reinhard Büttner
Institut für Pathologie,
Prof. Dr. med. Konrad Schackert
Abteilung für Chirurgische Forschung,
Universitätsklinikum Carl Gustav Carus,
Prof. Dr. med. Wolf H. Schmiegel
Conflict of interest statement
Between 1999 and 2011 the authors received funding from Deutsche Krebshilfe (German Cancer Aid), as part of the joint project Familial Colorectal Cancer.
Professor Schackert has received lecture fees from the German Society for Digestive and Metabolic Disorders (DGVS, Deutsche Gesellschaft für Verdauungs- und Stoffwechselerkrankungen) and consultancy fees from the Medical Care Unit at University Hospital Dresden.
Professor Schmiegel has received reimbursement of continuing education costs and travel expenses from the German Society for Digestive and Metabolic Disorders (DGVS, Deutsche Gesellschaft für Verdauungs- und Stoffwechselerkrankungen) and Falk. He has also received fees from Amgen, Apceth, AstraZeneca, Merck, Roche, Abbott, ECM, GSB, MedCongress, Pfizer, and Siemens Healthcare. Prof. Schmiegel holds several patents: PCT/DE2008/001220; DE102004063132.8–41; DE102006048249.2; DE102004036907.0–41; PCT/DE2007/002174; US61/176,353; DE102010046866.5; DE102011108254.2.
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