Identification of a novel kindred with familial pancreatitis and pancreatic cancer.
OBJECTIVE
Hereditary pancreatic cancer comprises about 10% of pancreatic cancer cases. Multiple causative mutations have been identified. Here we describe a pancreatitis/pancreatic cancer (P/PC) family, which demonstrates pancreatitis and pancreatic cancer resulting from an uncharacterized mutation.


METHODS
Family members completed evaluations to determine signs of mutation status. Select patients were screened for mutations associated with hereditary pancreatic diseases.


RESULTS
In generation II, 12 siblings exhibit 6 cases of pancreatitis, 3 pancreatic cancer, and 2 obligate carrier status. The average age at pancreatitis diagnosis of enrolled members is 32.5 years; average age at pancreatic cancer diagnosis is 59 years. There is no association with known cancer syndromes. Those affected generally present with mild epigastric pain, and CT scans demonstrate characteristic fatty infiltration of the pancreatic body and tail with sparing of the head and neck. Full sequence analysis of genes associated with hereditary pancreatic disease failed to demonstrate known mutations or polymorphisms.


CONCLUSIONS
Based upon pedigree evaluation and preliminary DNA analysis, we believe that the family members with P/PC carry a novel genetic mutation resulting in hereditary pancreatitis. This mutation is autosomal dominant, expressed with high penetrance, and is part of a unique hereditary syndrome that significantly increases pancreatic cancer risk.
LaFemina
Jennifer
J
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Roberts
Penelope A
PA
Hung
Yin P
YP
Gusella
James F
JF
Sahani
Dushyant
D
Fernández-del Castillo
Carlos
C
Warshaw
Andrew L
AL
Thayer
Sarah P
SP
D000428:Alcohol Drinking / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000000981:diagnostic imaging / Q000235:genetics; D002353:Carrier State; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D010195:Pancreatitis / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D035781:Siblings; D014026:Nicotiana / Q000009:adverse effects; D014057:Tomography, X-Ray Computed