GENETIC-COUNSELING IN HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER - AN EXTENDED FAMILY WITH MSH2 MUTATION

Objectives: Molecular genetic advances have increased the demand for D NA testing. We describe DNA based genetic counseling in a hereditary n onpolyposis colorectal cancer (HNPCC) family. Methods: This extended H NPCC family was found to harbor the MSH2 germline mutation. Family his tory, medical, and pathology documents enabled us to secure a high deg ree of verification that the kindred qualified as HNPCC. DNA testing r evealed the MSH2 germline mutation that was verified independently in two laboratories. Genetic counseling was provided before DNA testing a nd disclosure of MSH2 findings. Results: Genetic counseling revealed a variety of findings characterized by emotional stress in MSH2 germlin e mutation carriers. Concerns centered around reproductive issues, pot ential transmission of the deleterious gene to their progeny, and disc rimination by insurance carriers and employers. More than one-half of the patients found to harbor the MSH2 mutation considered the option o f prophylactic subtotal colectomy. Conclusion: DNA testing should be r estricted to well-verified candidate families in which genetic counsel ing should be mandatory. HNPCC family members sought genetic risk asse ssment for their own health and that of their children. Contrasting em otional responses took place when told of their gene testing status an d this required a sensitive empathetic listening ear. Patients have ma ny concerns about their lifetime cancer destiny when told that they ha rbor the culprit MSH2 germline mutation.