Primary and Secondary Screening in individuals with Inherited Pancreatic Disease syndromes for Pancreatic ductal adenocarcinoma and complications of other pancreatic diseases.

Inclusion Criteria for Registry: Cancer families: Two first degree relatives with pancreatic adenocarcinoma. A family with three or more relatives with pancreatic ductal adenocarcinoma. Families with pancreatic cancer and other cancers (e.g. bowel, breast/ovarian, melanoma, gastric) that suggest a known cancer predisposition syndrome: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Familial atypical mole melanoma (FAMMM). Lynch Syndrome. Breast Ovarian Cancer Peutz-Jegher's syndrome Li Fraumeni syndrome Families with a causative mutation in a gene linked to pancreatic cancer (e.g. PALB2 BRCA2 or genes prospectively discovered to be linked to pancreatic cancers) and at least one case of pancreatic cancer in the family. Pancreatitis families: Families with two or more relatives with idiopathic pancreatitis. Families with at least one case of pancreatitis and a confirmed causative mutation in the PRSS1 gene. Cyst surveillance: Individuals already enrolled on surveillance due to identification of a pancreatic cystic lesion NOD individuals: Individuals over the age of 40 with diabetes mellitus diagnosed in the last 6 months Disease control Individuals with: diagnosed pancreatic ductal adenocarcinoma; acute or chronic pancreatitis of any aetiology; and individuals with long term (over two years) type 2 or 3c diabetes mellitus Inclusion Criteria for Screening: Individuals over 40 years of age from an established pancreatic cancer family where the family is consistent with predisposition with high penetrant autosomal dominant inheritance (for example, at least two first degree relatives with pancreatic ductal adenocarcinoma, where no non-penetrant carriers have to be assumed over the age of 75). Individuals with Peutz-Jeghers syndromes, or individuals with affected relatives under the age of 50 will be considered for inclusion below the age of 40. Unaffected members of a family with an associated cancer syndrome and at least one case of pancreatic cancer, who are over 40 years of age and who have been shown to carry the relevant genetic alteration. Any member of a Hereditary Pancreatitis (HP) family (autosomal dominant predisposition for pancreatitis) who have been confirmed to carry a causative PRSS1 mutation or (where no causative mutation is known) have symptoms of pancreatitis. Individuals incidentally found to have cystic lesions or other clinical features that indicate an increased risk of pancreatic cancer may also be included. There will be adaptation to risk models as the study progresses to fit the needs of the study outcomes.

Any individual who is incapable of providing informed consent. For genetic testing: Any individual who does not consent to be informed of clinically significant results. Genetic testing specifically for research purposes at a specific locus with no actionable clinical significance can be carried out (e.g. for a polymorphism that may associate with disease but is not causative), but only with explicit consent from the individual. For screening: Individuals of less than 40 years of age or 10 years younger than the youngest case in the family will be excluded. Risk assessment will be made using progressively developed models any individual deemed to have less than 2% chance of developing PDAC in the next three years will be excluded (this will depend on the evidence supporting the models and the exclusion will only apply if the steering committee agrees on the risk assessment). Any female participant able to bear a child but who has not taken appropriate contraceptive measures.