Insights into the genetic risk factors for the development of pancreatic disease

被引:28
作者
Zator, Zachary [2 ]
Whitcomb, David C. [1 ]
机构
[1] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Dept Med, Gastroenterol,Dept Human Genet,Dept Cell Biol & M, Room 401-4,3708 Fifth Ave, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA
基金
美国国家卫生研究院;
关键词
pancreatic disease; precision medicine; chronic pancreatitis; genetic; modeling; acute pancreatitis; diabetes; exocrine pancreatic insufficiency; IDIOPATHIC CHRONIC-PANCREATITIS; ALCOHOLIC CHRONIC-PANCREATITIS; HUMAN CATIONIC TRYPSINOGEN; RECURRENT ACUTE-PANCREATITIS; CLDN2-MORC4 LOCI ASSOCIATE; CYSTIC-FIBROSIS GENE; HEREDITARY PANCREATITIS; CIGARETTE-SMOKING; LONG-TERM; BICARBONATE PERMEABILITY;
D O I
10.1177/1756283X16684687
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Diseases of the exocrine pancreas such as recurrent acute pancreatitis (RAP), chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) represent syndromes defined according to traditional clinicopathologic criteria. The failure of traditional approaches to identify primary mechanisms underlying these progressive disorders illustrates a greater problem of failure of the germ theory of disease for complex disorders. Multiple genetic discoveries and new complex disease models force consideration of a new paradigm of 'precision medicine', requiring a new mechanistic definition of CP. Recognizing the advances in understanding complex gene and environment interactions, as well as the development of new strategies that limit or prevent the development of devastating end-stage diseases of the pancreas may lead to substantial improvements in patient care.
引用
收藏
页码:323 / 336
页数:14
相关论文
共 93 条
[51]   Is it long-term continuous drinking or the post-drinking withdrawal period that triggers the first acute alcoholic pancreatitis? [J].
Nordback, I ;
Pelli, H ;
Lappalainen-Lehto, R ;
Sand, J .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2005, 40 (10) :1235-1239
[52]   The Recurrence of Acute Alcohol-Associated Pancreatitis Can Be Reduced: A Randomized Controlled Trial [J].
Nordback, Isto ;
Pelli, Hanna ;
Lappalainen-Lehto, Riitta ;
Jarvinen, Satu ;
Raty, Sari ;
Sand, Juhani .
GASTROENTEROLOGY, 2009, 136 (03) :848-855
[53]   Type of CFTR Mutation Determines Risk of Pancreatitis in Patients With Cystic Fibrosis [J].
Ooi, Chee Y. ;
Dorfman, Ruslan ;
Cipolli, Marco ;
Gonska, Tanja ;
Castellani, Carlo ;
Keenan, Katherine ;
Freedman, Steven D. ;
Zielenski, Julian ;
Berthiaume, Yves ;
Corey, Mary ;
Schibli, Susanne ;
Tullis, Elizabeth ;
Durie, Peter R. .
GASTROENTEROLOGY, 2011, 140 (01) :153-161
[54]   Comprehensive screening of chymotrypsin C (CTRC) gene in tropical calcific pancreatitis identifies novel variants [J].
Paliwal, Sumit ;
Bhaskar, Seema ;
Mani, K. Radha ;
Reddy, D. Nageshwar ;
Rao, G. Venkat ;
Singh, Shivaram Prasad ;
Thomas, Varghese ;
Chandak, Giriraj Ratan .
GUT, 2013, 62 (11) :1602-1606
[55]   Dynamic Regulation of CFTR Bicarbonate Permeability by [Cl-]i and Its Role in Pancreatic Bicarbonate Secretion [J].
Park, Hyun Woo ;
Nam, Joo Hyun ;
Kim, Joo Young ;
Namkung, Wan ;
Yoon, Jae Seok ;
Lee, Jung-Soo ;
Kim, Kyung Sik ;
Venglovecz, Viktoria ;
Gray, Michael A. ;
Kim, Kyung Hwan ;
Lee, Min Goo .
GASTROENTEROLOGY, 2010, 139 (02) :620-631
[56]   Risk factors for recurrent acute alcohol-associated pancreatitis: A prospective analysis [J].
Pelli, Hanna ;
Lappalainen-Lehto, Riitta ;
Piironen, Anneli ;
Sand, Juhani ;
Nordback, Isto .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2008, 43 (05) :614-621
[57]   SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis [J].
Pfützer, RH ;
Barmada, MM ;
Brunskill, APJ ;
Finch, R ;
Hart, PS ;
Neoptolemos, J ;
Furey, WF ;
Whitcomb, DC .
GASTROENTEROLOGY, 2000, 119 (03) :615-623
[58]   Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection [J].
Raimondi, Sara ;
Lowenfels, Albert B. ;
Morselli-Labate, Antonio M. ;
Maisonneuve, Patrick ;
Pezzilli, Raffaele .
BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY, 2010, 24 (03) :349-358
[59]   Cigarette Smoke Induces Systemic Defects in Cystic Fibrosis Transmembrane Conductance Regulator Function [J].
Raju, S. Vamsee ;
Jackson, Patricia L. ;
Courville, Clifford A. ;
McNicholas, Carmel M. ;
Sloane, Peter A. ;
Sabbatini, Gina ;
Tidwell, Sherry ;
Tang, Li Ping ;
Liu, Bo ;
Fortenberry, James A. ;
Jones, Caleb W. ;
Boydston, Jeremy A. ;
Clancy, J. P. ;
Bowen, Larry E. ;
Accurso, Frank J. ;
Blalock, J. Edwin ;
Dransfield, Mark T. ;
Rowe, Steven M. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2013, 188 (11) :1321-1330
[60]   Calcium-dependent enzyme activation and vacuole formation in the apical granular region of pancreatic acinar cells [J].
Raraty, M ;
Ward, J ;
Erdemli, G ;
Vaillant, C ;
Neoptolemos, JP ;
Sutton, R ;
Petersen, OH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (24) :13126-13131