Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent data suggest that genetic alterations are relevant risk factors for chronic pancreatitis. The highest risk is associated with autosomal-dominant mutations (N29I, R122H) of the cationic trypsinogen (PRSS1). Further mutations were identified in the genes of the pancreatic trypsin inhibitor (SPINK1) and in the cystic fibrosis transmembrane conductance regulator (CFTR). A remarkable finding was that both molecules were also mutated in patients suffering from alcoholic chronic pancreatitis. According to recent estimations, genetic alterations may be regarded as more severe risk factors than chronic alcohol consumption. To identify patients with mutations, a positive family history could be of help, but mutations were also found in a significant number of those with a negative family history. On the other hand, in approximately 40% of the patients with a positive family history no mutations were found up to now. The age at onset is lower in patients with genetic risk factors; however, no clear limit can be denominated above which a screening is not appropriate. Therefore, in our department genetic screening is offered to all patients with chronic pancreatitis of unclear origin. There is no specific treatment in patients with a genetically based disease. The patients with familial pancreatitis-increased rates of pancreas cancer were described but there is no agreement concerning the prophylactic strategy. Prevention of cancer by routine pancreatectomy, though performed recently, is not justified at the moment. Clinical criteria may be more appropriate to decide the timing and the extent of the operation.
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PMID:Identification of patients with genetic risk factors of pancreatitis: impact on treatment and cancer prevention. 1475 25

Mutations in the cationic trypsinogen gene are acknowledged as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. However, whether patients with mutations in other genes, such as the serine protease inhibitor Kazal type 1 (SPINK1) gene, are also at a higher risk of pancreatic cancer remains unknown. We report a case of pancreatic cancer associated with chronic calcifying pancreatitis in a patient with a homozygous N34S mutation in the SPINK1 gene. A 44-year-old woman was hospitalized due to obstructive jaundice. Preoperative examination showed a tumor in the head of the pancreas and multiple pancreatic stones; pancreatoduodenectomy revealed a solid tumor, 3.0 x 2.5 cm in size, in the head of the pancreas, and numerous pancreatic stones throughout the pancreas. Pathologic studies revealed moderately differentiated tubular adenocarcinoma. Mutational analyses of the SPINK1 and PRSS1 genes in members of the patient's family were carried out. The homozygous N34S mutation in the SPINK1 gene was found in the patient and her older sister, who was previously diagnosed with chronic calcific pancreatitis and had undergone the Frey operation. The patient's parents and brother were unaffected carriers of the N34S heterozygous mutation. No family members had any mutations in the cationic trypsinogen gene. To our knowledge, this is the first reported case of chronic pancreatitis accompanied by pancreatic cancer in a patient with the SPINK1 N34S mutation. Although this case does not meet the classic criteria of hereditary pancreatitis, it does suggest that the SPINK1 N34S mutation may be associated with cancer development in patients with hereditary pancreatitis. Further prospective, multicenter trials investigating secondary screening for pancreatic cancer in hereditary pancreatitis are necessary to clarify the role of SPINK1 mutations in the development of pancreatic cancer.
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PMID:Hereditary pancreatitis as the premalignant disease: a Japanese case of pancreatic cancer involving the SPINK1 gene mutation N34S. 1508 77

Inflammatory disease of the pancreas falls into two major classifications: acute and chronic. Acute pancreatitis is a reversible process, whereas chronic pancreatitis produces irreversible changes in the architecture and function of the pancreas. The recent finding that mutations in the gene encoding cationic trypsinogen are associated with hereditary pancreatitis, the identification of genes that increase the risk for developing chronic pancreatitis, and advances in cell biology have contributed greatly to our understanding of the molecular mechanisms leading to pancreatitis. Although pancreatitis is less common in children than in adults, it still occurs with regularity and should be considered in any child with acute or chronic abdominal pain. The major difference between pancreatitis in children and adults lies in the etiologies and outcome of acute pancreatitis and in the etiology of chronic pancreatitis. The treatment of acute and chronic pancreatitis is similar at all ages.
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PMID:Pancreatitis in childhood. 1512 92

The pathogenesis of idiopathic chronic pancreatitis remains poorly understood despite the high expectations for ascribing the pancreatic damage in affected patients to genetic defects. Mutations in the cationic trypsinogen gene, pancreatic secretory trypsin inhibitor, and the cystic fibrosis conductance regulator gene do not account for the chronic pancreatitis noted in most patients with idiopathic chronic pancreatitis. Small duct chronic pancreatitis can be best diagnosed with a hormone stimulation test. Endoscopic ultrasonography can detect abnormalities in both the parenchyma and ducts of the pancreas. The true value of endoscopic ultrasonography in diagnosing small duct chronic pancreatitis remains to be fully defined and is under active investigation. It is not clear whether endoscopic ultrasonography is more sensitive for early structural changes in patients with small duct disease or is over diagnosing chronic pancreatitis. Pancreatic enzyme supplementation with non-enteric formulation along with acid suppression (H2 blockers or proton pump inhibitors) is an effective therapy for pain in patients with small duct chronic pancreatitis. The role of endoscopic ultrasonography-guided celiac plexus block should be limited to treating those patients with chronic pancreatitis whose pain has not responded to other modalities. Total pancreatectomy followed by autologous islet cell autotransplantation appears to be potential therapeutic approach but for now should be considered experimental.
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PMID:Chronic pancreatitis: controversies in etiology, diagnosis and treatment. 1550 8

Since the discovery of the cationic trypsinogen gene mutations in patients with hereditary pancreatitis, a variety of pancreatitis-associated gene mutations have been reported, including pancreatic secretory trypsin inhibitor and cystic fibrosis transmembrane conductance regulator. Although the patients with these mutations are rarely seen, genetic disorders inducing pancreatitis have provided us major breakthroughs to understand the molecular basis of the disease. Furthermore, the major stream in pancreatology has been evidenced in patients with hereditary pancreatitis: acute pancreatitis --> chronic pancreatitis --> pancreatic cancer. This report will focus on the pancreatitis-associated genes and the molecular mechanism of pancreatitis associating with these gene mutations.
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PMID:[Pancreatitis-associated gene mutations]. 1555 98

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.
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PMID:Genetic aspects of chronic pancreatitis. 1556 96

The identification of a specific mutation in the human cationic trypsinogen gene in large kindreds with hereditary pancreatitis was the key to understand the genetic background of chronic pancreatitis. Rapidly, other variants within the same gene were identified-even in small families with a minority of patients. Later, mutations of the most important intrapancreatic trypsin inhibitor SPINK1 were found with high prevalence in patients with idiopathic, tropical and alcoholic chronic pancreatitis. We summarize interesting genetic and biochemical findings, point to clinical features and review recommendations for genetic analysis, follow-up and cancer prevention.
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PMID:[Clinical implications of genetic risk factors of chronic pancreatitis]. 1565 84

Hereditary pancreatitis (HP) is an autosomal dominant inherited disease characterized by recurrent episodes of pancreatitis often beginning in childhood, a family history of at least 2 other affected members, and the absence of known etiologic factors. The discovery of mutations in cationic trypsinogen gene (PRSS1) in HP not only provided insights into the molecular mechanisms of pancreatitis, but also opened a new era in the field of chronic pancreatitis. The detection of mutations in serine protease inhibitor, Kazal type 1 (SPINK1) and CFTR in patients with hereditary or idiopathic chronic pancreatitis has placed the emphasis on the importance of genetic mutations in pancreatitis. Because the estimated cumulative risk of pancreatic cancer development in hereditary pancreatitis is nearly 40%, screening tests are important in selected cases. There are no specific medical therapies recommended in patients with HP. Registration of patients with Nationwise Registries is essential if management strategies are to be improved and genetic research to be continued.
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PMID:[Hereditary pancreatitis]. 1572 18

Gene conversion--the substitution of genetic material from another gene--is recognized as the underlying cause of a growing number of genetic diseases. While in most cases conversion takes place between a normal gene and its pseudogene, here we report an occurrence of disease-associated gene conversion between two functional genes. Chronic pancreatitis in childhood is frequently associated with mutations of the cationic trypsinogen gene (serine protease 1; PRSS1). We have analyzed PRSS1 in 1106 patients with chronic pancreatitis, and identified a novel conversion event affecting exon 2 and the subsequent intron. The recombination replaced at least 289 nucleotides with the paralogous sequence from the anionic trypsinogen gene (serine protease 2; PRSS2), and resulted in the PRSS1 mutations c.86A > T and c.161A > G, causing the amino acid substitutions N29I and N54S, respectively. Analysis of the recombinant N29I-N54S double mutant cationic trypsinogen revealed increased autocatalytic activation, which was solely due to the N29I mutation. In conclusion, we have demonstrated that gene conversion between two functional paralogous trypsinogen genes can occur and cause genetically determined chronic pancreatitis.
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PMID:Gene conversion between functional trypsinogen genes PRSS1 and PRSS2 associated with chronic pancreatitis in a six-year-old girl. 1577 35

The understanding of pathogenesis of acute and chronic pancreatitis has benefited from the progress made in genetic investigations. The discoveries of the gain of function mutations of cationic trypsinogen gene (PRSS1) and the loss of function mutations of pancreatic secretory trypsin inhibitor (SPINK 1) or other potential defects in genes that regulate pancreatic secretory function or modulate inflammatory response to pancreatic injury has changed our current concepts on the pathogenesis of pancreatitis. Genetic factors play an important role in the susceptibility to pancreatic injury, severity and evolution of inflammatory process, leading in some cases to chronic inflammation and/or fibrosis. Acute pancreatitis is viewed as an event and chronic pancreatitis as a process, sequentially linked, reflecting a complex interaction between genetic and environmental factors.
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PMID:Genetic factors in pancreatitis. 1580 Jun 94


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