Pancreatitis and Pancreatic Cancer

Posted by e-Medical PPT Wednesday, October 3, 2012
Outline
1.Origins of Pancreatitis
Premature trypsinogen activation
2. Genetics of Acute and Chronic Pancreatitis
Trypsinogen,SPINK1,CFTR
3.Pancreatic Cancer:Links with pancreatitis

Pancreatitis
Pancreas - an organ that makes bicarbonate to nutralize gastric acid, enzymes to digest the contents of a meal and insulin to signal the body to store ingested nutrients.
Acute Pancreatitis - An acute, potentially life-threatening condition presenting with severe abdominal pain in which the pancreas appears to digest itself.    It is usually caused by gallstones, alcohol or is idiopathic.
Chronic Pancreatitis - an irreversible scarring of the pancreas with permanent loss of pancreatic function that typically causes unrelenting abdominal pain.   
Hereditary Pancreatitis - a unusual form of acute and chronic pancreatitis that runs in families.  The risk of pancreatic cancer  is >50 times normal.

Hereditary Pancreatitis
Hereditary pancreatitis (HP) is an unusual form of acute and chronic pancreatitis that runs in families.  The risk of pancreatic cancer  is >50 times normal.
Although HP is only responsible for 2-3% of all cases of chronic pancreatitis, study of this disease has revolutionized our understanding of pancreatic diseases

PRSS1 Mutations - Overview
Two mutations are both common and disease-causing:  PRSS1 R122H and N29I (new numbers)
Individuals with either of the two mutations have about an 80% chance of developing acute pancreatitis.
Of those with acute pancreatitis, about half develop chronic pancreatitis
40% with chronic pancreatitis will develop pancreatic cancer by age 70 (smoking doubles risk)

SPINK1 Mutations - Overview
SPINK1/PSTI mutations are common in the population (~2%)
SPINK1/PSTI are clearly associated with ICP (~25%). 
The mutation associated risk is low (<1%). 
Modeling and familial clustering suggest that SPINK1 mutations are disease modifying.
SPINK1/PSTI mutations may lower the threshold for pancreatitis from other genetic or environmental factors, but by themselves are not disease causing
The N34S mutations has a world-wide distribution.
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