Genetic counseling and testing for germline p16 mutations in two pancreatic cancer-prone families

The mortality from pancreatic cancer coincides closely with its incidence, indicating a dismal outlook. Hereditary factors probably account for approx imately 5%-10% of the pancreatic cancer burden. The molecular genetic etiol ogy of pancreatic cancer is only beginning to be identified. We describe ou r genetic counseling experience with 2 large families prone to pancreatic c ancer-malignant melanoma in which p16 (CDKN2) germline mutations had been i dentified. Members of each family underwent intensive counseling before and at the time of disclosure of p16 germline mutation findings. Two non-cance r-affected siblings from each of the 2 families had p16 mutations identifie d in DNA from their peripheral blood lymphocytes. in each case, a parent af fected with pancreatic cancer also harbored the p16 mutation identified in DNA from their respective tumor blocks. The sibling pairs stated that they would seriously consider prophylactic pancreatectomy if biomarkers or imagi ng findings suggested a precancerous state. Our experience highlights limit ed options for managing these families and emphasizes the need for better t ools to diagnose pancreatic cancer at a curable stage.