Abstract
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.
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References
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Etemad B, Whitcomb DC. Chronic pancreatitis: Diagnosis, classification, and new genetic developments. Gastroenterology. 2001;120:682–707.
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.
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.
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.
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.
Chen JM, Ferec C. Chronic pancreatitis: genetics and pathogenesis. Annu Rev Genomics Hum Genet. 2009;10:63–87.
Whitcomb DC. Genetic aspects of pancreatitis. Annu Rev Med. 2010;61:413–24.
Larusch J, Whitcomb DC. Genetics of pancreatitis. Curr Opin Gastroenterol. 2011;27(5):467–74.
• 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.
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.
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.
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.
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.
•• 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.
• 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.
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.
•• 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.
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.
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.
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.
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.
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.
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.
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.
Thrower EC, Gorelick FS, Husain SZ. Molecular and cellular mechanisms of pancreatic injury. Curr Opin Gastroenterol. 2010;26(5):484–9.
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.
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.
Acknowledgements
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).
Disclosure
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.
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Solomon, S., Whitcomb, D.C. Genetics of Pancreatitis: An Update for Clinicians and Genetic Counselors. Curr Gastroenterol Rep 14, 112–117 (2012). https://doi.org/10.1007/s11894-012-0240-1
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DOI: https://doi.org/10.1007/s11894-012-0240-1