E-cadherin mutation-based genetic counseling and hereditary diffuse gastric carcinoma

The E-cadherin mutation has been identified in a subset of families with mu ltiple cases of diffuse gastric carcinoma. However, the true penetrance of this mutation and its association with other carcinomas in such families re mains elusive. We aim to show the importance of DNA-based genetic counselin g in hereditary diffuse gastric carcinoma. The proband was self-referred af ter three of his siblings died of diffuse gastric carcinoma. Medical and pa thology records confirmed diagnoses. The family was educated about diffuse gastric carcinoma. Analysis for the 70G -->T mutation was performed by sequ encing genomic DNA from lymphocyte pellets. DNA results and genetic counsel ing were provided individually to those tested. Twenty-four family members were tested for the E-cadherin mutation. Nine were found to be positive and 15 were negative. Three who tested positive and were affected are now dece ased. None of the 19 patients counseled wanted results sent to their physic ians once they recognized the potential for insurance discrimination. None had undergone endoscopic ultrasound. Three who were positive for the E-cadh erin mutation expressed strong interest in prophylactic gastrectomy. The E- cadherin mutation strongly predicts susceptibility to diffuse gastric carci noma. Emotional stress in at-risk patients, the limited knowledge of the mu tation's penetrance, and limitations of available screening mandate patient -centered genetic counseling. (C) 2000 Elsevier Science Inc. All rights res erved.