Genetic aspects of chronic pancreatitis

The classical feature of hereditary pancreatitis (HP) is characterized by recurrent episodes of acute pancreatitis or a priori chronic pancreatitis in several members of one family. In 1996, the identification of the first HP-associated mutation in the cationic trypsinogen gene provided a breakthrough in our understanding of the pathogenesis of chronic pancreatitis. In the following years, several different mutations in the same gene have been found in a large number of investigated families. Most intriguing, HP patients have a more than 50-fold increased risk of pancreatic ductal cancer in comparison with expected pancreatic cancers in the general population. Variants of the major intrapancreatic trypsin antagonist SPINK1 have implications for more common forms of chronic pancreatitis. Research has focussed on the SPINK1-N34S-mutation, which is closely associated with tropical, alcoholic, or "idiopathic" chronic pancreatitis. Chronic pancreatitis represents a variable part of the cystic fibrosis syndrome, which is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Several groups have reported an increased prevalence of CFTR mutations in patients with chronic pancreatitis of different etiology. In this review, we summarize interesting clinical and biochemical features of genetic variants in these genes which are associated with chronic pancreatitis.