Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden)

Familial atypical multiple mole melanoma (FAMMM) is an autosomal dominant d isease characterized by the familiar occurrence of malignant melanoma of th e skin and multiple atypical precursor lesions, Germline mutations in the p 16 (CDKN2A) gene have been reported in at least a quarter of such families. An association has been reported between p16 mutations and pancreatic canc er, The aim of this study was to assess the risk of developing pancreatic a nd other cancers in Dutch FAMMM families with a 19 bp deletion in exon 2 of the p16 gene (p16-Leiden). Mutation analysis was performed in 27 families suspected of FAMMM. Clinical and pathological data were collected from all relatives affected with cancer. A p16-Leiden mutation was identified in 19 families. These families included 86 patients with melanoma, The second mos t frequent cancer was pancreatic cancer, which was observed in 15 patients from 7 families. The mean age at diagnosis of pancreatic cancer was 58 year s (range 38-77 years). The estimated cumulative risk of developing pancreat ic cancer in putative mutation carriers by age 75 years was 17%, In 8 p16-L eiden-negative families, no cases of pancreatic cancer occurred. p16 mutati on carriers have a considerable risk of developing pancreatic cancer. Furth er studies should evaluate the value of surveillance of the pancreas in the se high-risk families. Int. J. Cancer 87:809-811, 2000, (C) 2000 Wiley-Liss , Inc.