Current Gastroenterology Reports

, Volume 14, Issue 2, pp 112–117 | Cite as

Genetics of Pancreatitis: An Update for Clinicians and Genetic Counselors

Pancreas (CE Forsmark, Section Editor)


With novel genetic technologies available, there is a paradigm shift in the way that risk assessments, diagnoses, and therapies for genetic susceptibility syndromes are addressed. Hereditary pancreatitis is among these conditions, for which genetic counseling and next generation sequencing, help families better understand, cope with and live healthier lives. Identifying a genetic etiology to a condition formally believed to be solely environmentally induced can alter the path for treatment for many patients. This finding introduces the concept of gene-environment interactions in human disease and the relationship between genetic predisposition and exposure risk in disease development. The genetic counseling process is complex with medical explanations, psychosocial issues relating to coping with diagnosis, potential future health problems, recurrence risks and family planning. These sometimes difficult conversations can be facilitated by a genetic counselor as a member of the multidisciplinary team. This chapter addresses the intricate medical and psychosocial issues that can arise in the setting of treating patients with hereditary pancreatitis.


Hereditary pancreatitis Acute pancreatitis Chronic pancreatitis Genetic counseling Genetic counselor Psychosocial Genetic testing Risk assessment Family history PRSS1 SPINK1 CFTR CTRC CASR Personalized medicine Next generation sequencing Whole genome/exome sequencing Gene-environment interactions 



Dr Whitcomb has been supported by the Wayne Fusaro Pancreatic Cancer Research Fund, The Frieda G. and Saul F. Shapira BRCA Cancer Research Program and the National Institutes of Health (DK061451, DK075803, DK054709).


S. Solomon is an employee of the University of Pittsburgh; Dr. D. Whitcomb is a board member for the National Pancreas Foundation and the Cooperative Alliance for Pancreatic Research, a consultant for Abbott, Millennium, and Lilly Pharmaceuticals, and an employee of the University of Pittsburgh. He has received grant funding from the NIIT, honoraria for CME Programs, stock options and royalties from Ambry Genetics, and payment for development of educational presentations from Abbott.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Etemad B, Whitcomb DC. Chronic pancreatitis: Diagnosis, classification, and new genetic developments. Gastroenterology. 2001;120:682–707.PubMedCrossRefGoogle Scholar
  2. 2.
    Pandol SJ, Gukovsky I, Satoh A, Lugea A, Gukovskaya AS. Emerging concepts for the mechanism of alcoholic pancreatitis from experimental models. J Gastroenterol. 2003;38(7):623–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Witt H, Apte MV, Keim V, Wilson JS. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology. 2007;132(4):1557–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Shanbhogue AK, Fasih N, Surabhi VR, Doherty GP, Shanbhogue DK, Sethi SK. A clinical and radiologic review of uncommon types and causes of pancreatitis. Radiographics. 2009;29(4):1003–26.PubMedCrossRefGoogle Scholar
  5. 5.
    Whitcomb DC, Yadav D, Adam S, Hawes RH, Brand RE, Anderson MA, et al. Multicenter approach to recurrent acute and chronic pancreatitis in the United States: the North American Pancreatitis Study 2 (NAPS2). Pancreatology. 2008;8(4–5):520–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Chen JM, Ferec C. Chronic pancreatitis: genetics and pathogenesis. Annu Rev Genomics Hum Genet. 2009;10:63–87.PubMedCrossRefGoogle Scholar
  7. 7.
    Whitcomb DC. Genetic aspects of pancreatitis. Annu Rev Med. 2010;61:413–24.PubMedCrossRefGoogle Scholar
  8. 8.
    Larusch J, Whitcomb DC. Genetics of pancreatitis. Curr Opin Gastroenterol. 2011;27(5):467–74.PubMedCrossRefGoogle Scholar
  9. 9.
    • Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nature Genetics. 1996;14(2):141–5. This paper reports the identification of the PRSS1 as an implicator in hereditary pancreatitis. PubMedCrossRefGoogle Scholar
  10. 10.
    Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, et al. Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol. 2004;2(3):252–61.PubMedCrossRefGoogle Scholar
  11. 11.
    Rebours V, Levy P, Ruszniewski P. An overview of hereditary pancreatitis. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2011 Sep 8.Google Scholar
  12. 12.
    Masson E, Le Marechal C, Delcenserie R, Chen JM, Ferec C. Hereditary pancreatitis caused by a double gain-of-function trypsinogen mutation. Hum Genet. 2008;123(5):521–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Applebaum SE, O’Connell JA, Aston CE, Whitcomb DC. Motivations and concerns of patients with access to genetic testing for hereditary pancreatitis. Am J Gastroenterol. 2001;96(5):1610–7.CrossRefGoogle Scholar
  14. 14.
    •• Ellis I, Lerch MM, Whitcomb DC, Committee C. Genetic Testing for Hereditary Pancreatitis: Guidelines for indications, counseling, consent and privacy issues. Pancreatology. 2001;1(5):401–11. The paper illustrates the issues relating to genetic testing for hereditary pancreatitis.CrossRefGoogle Scholar
  15. 15.
    • Wilfond BS. Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. American Society of Human Genetics Board of Directors, American College of Medical Genetics Board of Directors. American journal of human genetics. 1995 Nov;57(5):1233–41. This paper describes issues as they relate to testing minor for genetic conditions.Google Scholar
  16. 16.
    Depristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011;43(5):491–8.PubMedCrossRefGoogle Scholar
  17. 17.
    •• Schneider A, Larusch J, Sun X, Aloe A, Lamb J, Hawes R, et al. Combined Bicarbonate Conductance-Impairing Variants in CFTR and SPINK1 Variants Are Associated With Chronic Pancreatitis in Patients Without Cystic Fibrosis. Gastroenterology. 2011;140(1):162–71. This paper describes a prototype CFTR variant, R75Q that disrupts bicarbonate secretion and targets the pancreas, but not lung, for injury. It also provides insight into the interaction between CFTR and SPINK1 in pancreatic diseases. PubMedCrossRefGoogle Scholar
  18. 18.
    Khalid A, Finkelstein S, Thompson B, Kelly L, Hanck C, Godfrey TE, et al. A 93 year old man with the PRSS1 R122H mutation, low SPINK1 expression, and no pancreatitis: insights into phenotypic non-penetrance. Gut. 2006;55(5):728–31.PubMedCrossRefGoogle Scholar
  19. 19.
    Pfutzer RH, Barmada MM, Brunskill AP, Finch R, Hart PS, Neoptolemos J, et al. SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis. Gastroenterology. 2000;119(3):615–23.PubMedCrossRefGoogle Scholar
  20. 20.
    Threadgold J, Greenhalf W, Ellis I, Howes N, Lerch MM, Simon P, et al. The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease. Gut. 2002;50(5):675–81.PubMedCrossRefGoogle Scholar
  21. 21.
    Aoun E, Chang CC, Greer JB, Papachristou GI, Barmada MM, Whitcomb DC. Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis. PLoS One. 2008;3(4):e2003.PubMedCrossRefGoogle Scholar
  22. 22.
    Aoun E, Muddana V, Papachristou GI, Whitcomb DC. SPINK1 N34S is strongly associated with recurrent acute pancreatitis but is not a risk factor for the first or sentinel acute pancreatitis event. Am J Gastroenterol. 2010;105(2):446–51.PubMedCrossRefGoogle Scholar
  23. 23.
    Noone PG, Zhou Z, Silverman LM, Jowell PS, Knowles MR, Cohn JA. Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations. Gastroenterology. 2001;121(6):1310–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Felderbauer P, Klein W, Bulut K, Ansorge N, Dekomien G, Werner I, et al. Mutations in the calcium-sensing receptor: a new genetic risk factor for chronic pancreatitis? Scand J Gastroenterol. 2006;41(3):343–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Thrower EC, Gorelick FS, Husain SZ. Molecular and cellular mechanisms of pancreatic injury. Curr Opin Gastroenterol. 2010;26(5):484–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Namkung W, Han W, Luo X, Muallem S, Cho KH, Kim KH, et al. Protease-activated receptor 2 exerts local protection and mediates some systemic complications in acute pancreatitis. Gastroenterology. 2004;126(7):1844–59.PubMedCrossRefGoogle Scholar
  27. 27.
    Bhoomagoud M, Jung T, Atladottir J, Kolodecik TR, Shugrue C, Chaudhuri A, et al. Reducing Extracellular pH Sensitizes the Acinar Cell to Secretagogue-Induced Pancreatitis Responses in Rats. Gastroenterology. 2009 May 18.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Gastroenterology, Hepatology and Nutrition, Department of MedicineUniversity of PittsburghPittsburghUSA
  2. 2.Department of Cell Biology and Molecular PhysiologyUniversity of PittsburghPittsburghUSA
  3. 3.Department of Human GeneticsUniversity of PittsburghPittsburghUSA
  4. 4.GI AdministrationPittsburghUSA

Personalised recommendations