title: [Chronic pancreatitis--pancreas cancer: influence of genetic factors].
abstract: Chronic pancreatitis: Only recently mutations in several genes were found in patients with chronic pancreatitis. In those with a familial chronic pancreatitis mutations of the cationic trypsinogen were identified and the variants N29I and R122H lead to an autosomal dominant disease. In this group of patients the mutation N34S of the trypsin inhibitor SPINK1 was detected. In so-called idiopathic pancreatitis both variants of the SPINK1 and of the CFTR (cystic fibrosis transmembrane conductance regular) were identified. Alterations in both genes were also found in patients with alcoholic chronic pancreatitis. The strongest risk factor for chronic pancreatitis were trypsinogen mutations N29I and R122H mutations. However, both SPINK1 and CFTR increased the risk for chronic pancreatitis to a higher level than alcohol consumption. A genetic investigation should be performed in familial disease and younger age, but also in patients without family history and higher age a mutation could be found. Pancreas cancer: In 10% of the patients with pancreas cancer other members of the family were affected from the disease. Some of them belong to well characterized familial syndroms like HNPCC or Peutz-Jeghers-syndrom. In a minority of the others a genetic factor may be found, too. In sporadic disease the development of the tumor is characterized by continued acquirement of genetic alterations described by the PanIN model (pancreatic intraepithelial neoplesia). This means that the evolution of the neoplasia progresses from normal tissue via epithelial hyperplasy (PanIN 1A), papillary hyperplasy without (PanIN 1B) and with dysplasy (PanIN 2) and carcinoma in situ (PanIN 3) to invasive pancreas cancer. The progression is associated with genetic alterations of the cells (mutations of ki-ras, p16, p53 etc.). This results in deterioration of control of the cell cycle and the apoptosis and explains the malignancy of the disease. These findings may be used in the future to develop newer therapeutic principles in order to improve the dismal prognosis of this disease.
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig AöR. keimv@medizin.uni-leipzig.de
authors.forename: V
authors.initials: V
authors.lastname: Keim
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002908:Chronic Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004252:DNA Mutational Analysis; D004198:Disease Susceptibility; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010195:Pancreatitis / Q000235:genetics*; D019512:Pancreatitis, Alcoholic / Q000235:genetics; D012307:Risk Factors; D014357:Trypsin / Q000235:genetics; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin