Some of these, such as hereditary pancreatitis, are organ specific. Other syndromes, such as ataxia telangiectasia and Peutz-Jegher's Syndrome, are associated with the development of tumors at many sites in addition to the pancreas. Although pancreatic adenocarcinoma is a relatively rare in some of these genetic diseases, it's lethality makes it a clinically important complication of these syndromes. The precise risk of developing pancreatic adenocarcinoma is difficult to define in most of these syndromes but available relative risk data is summarized in table 1. Predisposition to pancreatic adenocarcinoma may be due to chronic injury and regeneration by analogy to patients with nonhereditary chronic pancreatitis.
Tumors usually develop later in life with an age distribution similar to that of sporadic tumors.
Ataxia telangiectasia is an autosomal recessive disorder. The gene responsible for the disorder resides on chromosome 11q22-23 and encodes for a protein similar to phosphatidylinositol 3' kinase which is involved in signal transduction, meiotic recombination and cell cycle control. Loss of one normal allele of this gene results in cells that are deficient in DNA repair and are prone to accumulate gene mutations. Patients are thus predisposed to many different types of cancers including leukemias, breast cancer, gastric cancers and pancreatic adenocarcinomas. This syndrome appears to be genetically heterogeneous with some but not all kindreds having germline mutations in the p16INK4a gene.