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Familial Pancreatic Cancer

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Pancreatic Cancer

Abstract

Inherited genetic changes, from high-penetrance mutations to common genetic variants of modest effect, play a significant role in pancreatic cancer risk both in the familial and nonfamilial forms of the disease. Approximately 20% of the familial clustering of pancreatic cancer is explained by inherited mutations in BRCA2, BRCA1, CDKN2A, PALB2, ATM, PRSS1, STK11, MLH1, MSH2, MHS6, and PMS2. Even among families without an identifiable germline mutation, the presence of a family history of pancreatic cancer is a strong risk factor for the development of pancreatic cancer. Given the substantial increased risk of pancreatic cancer associated with a family history, many clinical trials aimed at the early detection of pancreatic cancer in this population are underway. The goal of this chapter is to review the evidence supporting the importance of a family history of pancreatic cancer as a risk factor for pancreatic cancer and the clinical and pathological features of familial pancreatic cancer.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. https://doi.org/10.3322/caac.21332. PubMed PMID: 26742998.

    Article  PubMed  Google Scholar 

  2. SEER Cancer Statistics Review, 1975–2008 [Internet]. Bethesda: National Cancer Institute. Available from: http://seer.cancer.gov/csr/1975_2008/, based on Nov 2010 SEER data submission, posted to the SEER web site, 2011.

  3. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21. https://doi.org/10.1158/0008-5472.CAN-14-0155. PubMed PMID: 24840647.

    Article  CAS  PubMed  Google Scholar 

  4. Brune KA, Lau B, Palmisano E, Canto M, Goggins MG, Hruban RH, et al. Importance of age of onset in pancreatic cancer kindreds. J Natl Cancer Inst. 2010;102(2):119–26. https://doi.org/10.1093/jnci/djp466. Epub 2010/01/14. PubMed PMID: 20068195; PubMed Central PMCID: PMC2808346.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Klein AP, Brune KA, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJ, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004;64(7):2634–8. Epub 2004/04/03. PubMed PMID: 15059921.

    Article  CAS  PubMed  Google Scholar 

  6. Hruban RH, Canto MI, Goggins M, Schulick R, Klein AP. Update on familial pancreatic cancer. Adv Surg. 2010;44:293–311. Epub 2010/10/06. PubMed PMID: 20919528; PubMed Central PMCID: PMC2966038.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hruban RH, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJ, Falatko F, et al. Familial pancreatic cancer. Ann Oncol. 1999;10(Suppl 4):69–73. PubMed PMID: HRUBAN1999.

    Article  PubMed  Google Scholar 

  8. Klein AP, Beaty TH, Bailey-Wilson JE, Brune KA, Hruban RH, Petersen GM. Evidence for a major gene influencing risk of pancreatic cancer. Genet Epidemiol. 2002;23(2):133–49. https://doi.org/10.1002/gepi.1102. Epub 2002/09/06. PubMed PMID: 12214307.

    Article  PubMed  Google Scholar 

  9. Childs EJ, Chaffee KG, Gallinger S, Syngal S, Schwartz AG, Cote ML, et al. Association of common susceptibility variants of pancreatic cancer in higher-risk patients: a PACGENE study. Cancer Epidemiol Biomark Prev. 2016;25(7):1185–91. https://doi.org/10.1158/1055-9965.EPI-15-1217. PubMed PMID: 27197284.

    Article  CAS  Google Scholar 

  10. Falk RT, Pickle LW, Fontham ET, Correa P, Fraumeni JF. Life-style risk factors for pancreatic cancer in Louisiana: a case-control study. Am J Epidemiol. 1988;128(2):324–36. PubMed PMID: FALK1988.

    Article  CAS  PubMed  Google Scholar 

  11. Friedman GD, Van Den Eeden SK. Risk factors for pancreatic cancer: an exploratory study. Int J Epidemiol. 1993;22:30–7. PubMed PMID: 5.

    Article  CAS  PubMed  Google Scholar 

  12. Fernandez E, La Vecchia C, d’Avanzo B, Negri E, Franceschi S. Family history and the risk of liver, gallbladder, and pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 1994;3(3):209–12. PubMed PMID: FERNANDEZ1994.

    CAS  PubMed  Google Scholar 

  13. Price TF, Payne RL, Oberleitner MG. Familial pancreatic cancer in south Louisiana. Cancer Nurs. 1996;19(4):275–82. PubMed PMID: PRICE1996.

    Article  CAS  PubMed  Google Scholar 

  14. Ghadirian P, Boyle P, Simard A, Baillargeon J, Maisonneuve P, Perret C. Reported family aggregation of pancreatic cancer within a population- based case-control study in the Francophone community in Montreal, Canada. Int J Pancreatol. 1991;10(3–4):183–96. PubMed PMID: GHADIRIAN1991A.

    CAS  PubMed  Google Scholar 

  15. Coughlin SS, Calle EE, Patel AV, Thun MJ. Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control. 2000;11(10):915–23. PubMed PMID: COUGHLIN2000.

    Article  CAS  PubMed  Google Scholar 

  16. Schenk M, Schwartz AG, O’Neal E, Kinnard M, Greenson JK, Fryzek JP, et al. Familial risk of pancreatic cancer. J Natl Cancer Inst. 2001;93(8):640–4. PubMed PMID: SCHENK2001.

    Article  CAS  PubMed  Google Scholar 

  17. Silverman DT. Risk factors for pancreatic cancer: a case-control study based on direct interviews. Teratog Carcinog Mutagen. 2001;21(1):7–25. PubMed PMID: SILVERMAN2001.

    Article  CAS  PubMed  Google Scholar 

  18. Jacobs EJ, Chanock SJ, Fuchs CS, Lacroix A, McWilliams RR, Steplowski E, et al. Family history of cancer and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan). Int J Cancer. 2010;127(6):1421–8. https://doi.org/10.1002/ijc.25148. Epub 2010/01/06. PubMed PMID: 20049842; PubMed Central PMCID: PMC2926939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Silverman DT, Schiffman M, Everhart J, Goldstein A, Lillemoe KD, Swanson GM, et al. Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer. 1999;80(11):1830–7. https://doi.org/10.1038/sj.bjc.6690607. Epub 1999/09/01. PubMed PMID: 10468306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Petersen GM, de Andrade M, Goggins M, Hruban RH, Bondy M, Korczak JF, et al. Pancreatic cancer genetic epidemiology consortium. Cancer Epidemiol Biomark Prev. 2006;15(4):704–10. https://doi.org/10.1158/1055-9965.EPI-05-0734. Epub 2006/04/15. PubMed PMID: 16614112.

    Article  Google Scholar 

  21. Wang L, Brune KA, Visvanathan K, Laheru D, Herman J, Wolfgang C, et al. Elevated cancer mortality in the relatives of patients with pancreatic cancer. Cancer Epidemiol Biomark Prev. 2009;18(11):2829–34. https://doi.org/10.1158/1055-9965.EPI-09-0557. Epub 2009/10/22. PubMed PMID: 19843679; PubMed Central PMCID: PMC3190638.

    Article  Google Scholar 

  22. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and heritable factors in the causation of cancer – analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000;343(2):78–85. PubMed PMID: LICHTENSTEIN2000.

    Article  CAS  PubMed  Google Scholar 

  23. Lynch HT, Smyrk T, Lynch J, Fitzgibbons Jr R, Lanspa S, McGinn T. Update on the differential diagnosis, surveillance and management of hereditary non-polyposis colorectal cancer. Eur J Cancer. 1995;31A(7–8):1039–46. PubMed PMID: 7576988.

    Article  CAS  PubMed  Google Scholar 

  24. Vasen HF, Hendriks Y, de Jong AE, van Puijenbroek M, Tops C, Brocker-Vriends AH, et al. Identification of HNPCC by molecular analysis of colorectal and endometrial tumors. Dis Markers. 2004;20(4–5):207–13. PubMed PMID: 15528786; PubMed Central PMCID: PMCPMC3839268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lakhani SR, Easton DF, Stratton MR, StorferIsser A, Anderson TJ, Farid LM, et al. Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Lancet. 1997;349(9064):1505–10. PubMed PMID: WOS:A1997XA90100009.

    Article  Google Scholar 

  26. Singhi AD, Ishida H, Ali SZ, Goggins M, Canto M, Wolfgang CL, et al. A histomorphologic comparison of familial and sporadic pancreatic cancers. Pancreatology. 2015;15(4):387–91. https://doi.org/10.1016/j.pan.2015.04.003. PubMed PMID: 25959245; PubMed Central PMCID: PMCPMC4515195.

    Article  PubMed  Google Scholar 

  27. Norris AL, Roberts NJ, Jones S, Wheelan SJ, Papadopoulos N, Vogelstein B, et al. Familial and sporadic pancreatic cancer share the same molecular pathogenesis. Familial Cancer. 2015;14(1):95–103. https://doi.org/10.1007/s10689-014-9755-y. PubMed PMID: 25240578; PubMed Central PMCID: PMCPMC4357548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shi C, Klein AP, Goggins M, Maitra A, Canto M, Ali S, et al. Increased prevalence of precursor lesions in familial pancreatic cancer patients. Clin Cancer Res. 2009;15(24):7737–43. https://doi.org/10.1158/1078-0432.CCR-09-0004. Epub 2009/12/10. PubMed PMID: 19996207; PubMed Central PMCID: PMC2795080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Klein AP. Identifying people at a high risk of developing pancreatic cancer. Nat Rev Cancer. 2013;13(1):66–74. https://doi.org/10.1038/nrc3420. Epub 2012/12/12. PubMed PMID: 23222481; PubMed Central PMCID: PMC3649844.

    Article  CAS  PubMed  Google Scholar 

  30. Roberts NJ, Klein AP. Genome-wide sequencing to identify the cause of hereditary cancer syndromes: with examples from familial pancreatic cancer. Cancer Lett. 2013;340(2):227–33. https://doi.org/10.1016/j.canlet.2012.11.008. Epub 2012/12/01. PubMed PMID: 23196058; PubMed Central PMCID: PMC3652916.

    Article  CAS  PubMed  Google Scholar 

  31. Roberts NJ, Norris AL, Petersen GM, Bondy ML, Brand R, Gallinger S, et al. Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer. Cancer Discov. 2016;6(2):166–75. https://doi.org/10.1158/2159-8290.CD-15-0402. PubMed PMID: 26658419; PubMed Central PMCID: PMCPMC4744563.

    Article  CAS  PubMed  Google Scholar 

  32. Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol. 2008;9(10):759–69. https://doi.org/10.1038/nrm2514. PubMed PMID: 18813293.

    Article  CAS  PubMed  Google Scholar 

  33. Roberts NJ, Jiao Y, Yu J, Kopelovich L, Petersen GM, Bondy ML, et al. ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov. 2012;2(1):41–6. https://doi.org/10.1158/2159-8290.CD-11-0194. Epub 2012/05/16. PubMed PMID: 22585167; PubMed Central PMCID: PMC3676748.

    Article  CAS  PubMed  Google Scholar 

  34. Yang XR, Rotunno M, Xiao Y, Ingvar C, Helgadottir H, Pastorino L, et al. Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations. Hum Genet. 2016;135(11):1241–9. https://doi.org/10.1007/s00439-016-1715-1. PubMed PMID: 27449771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hu C, Hart SN, Bamlet WR, Moore RM, Nandakumar K, Eckloff BW, et al. Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients. Cancer Epidemiol Biomark Prev. 2016;25(1):207–11. https://doi.org/10.1158/1055-9965.EPI-15-0455. PubMed PMID: 26483394; PubMed Central PMCID: PMCPMC4754121.

    Article  CAS  Google Scholar 

  36. Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012;491(7424):399–405. https://doi.org/10.1038/nature11547. PubMed PMID: 23103869; PubMed Central PMCID: PMCPMC3530898.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Petersen GM, et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 1996;56(23):5360–4. PubMed PMID: GOGGINS1996.

    CAS  PubMed  Google Scholar 

  38. Murphy KM, Brune KA, Griffin C, Sollenberger JE, Petersen GM, Bansal R, et al. Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%. Cancer Res. 2002;62(13):3789–93. PubMed PMID: MURPHY2002.

    CAS  PubMed  Google Scholar 

  39. Hahn SA, Greenhalf B, Ellis I, Sina-Frey M, Rieder H, Korte B, et al. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst. 2003;95(3):214–21. PubMed PMID: HAHN2003.

    Article  CAS  PubMed  Google Scholar 

  40. Couch FJ, Johnson MR, Rabe KG, Brune K, de Andrade M, Goggins M, et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomark Prev. 2007;16(2):342–6. https://doi.org/10.1158/1055-9965.EPI-06-0783. Epub 2007/02/16. PubMed PMID: 17301269.

    Article  CAS  Google Scholar 

  41. Holter S, Borgida A, Dodd A, Grant R, Semotiuk K, Hedley D, et al. Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma. J Clin Oncol. 2015;33(28):3124–9. https://doi.org/10.1200/JCO.2014.59.7401. PubMed PMID: 25940717.

    Article  CAS  PubMed  Google Scholar 

  42. Ferrone CR, Levine DA, Tang LH, Allen PJ, Jarnagin W, Brennan MF, et al. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J Clin Oncol. 2009;27(3):433–8. https://doi.org/10.1200/JCO.2008.18.5546. Epub 2008/12/10. JCO.2008.18.5546 [pii]. PubMed PMID: 19064968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. The breast cancer linkage consortium. J Natl Cancer Inst. 1999;91(15):1310–6. PubMed PMID: ANON1999.

    Article  Google Scholar 

  44. Mocci E, Milne RL, Mendez-Villamil EY, Hopper JL, John EM, Andrulis IL, et al. Risk of pancreatic cancer in breast cancer families from the breast cancer family registry. Cancer Epidemiol Biomark Prev. 2013;22(5):803–11. https://doi.org/10.1158/1055-9965.EPI-12-0195. PubMed PMID: 23456555; PubMed Central PMCID: PMCPMC3739843.

    Article  CAS  Google Scholar 

  45. Zhen DB, Rabe KG, Gallinger S, Syngal S, Schwartz AG, Goggins MG, et al. BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. Genet Med. 2015;17(7):569–77. https://doi.org/10.1038/gim.2014.153. PubMed PMID: 25356972; PubMed Central PMCID: PMCPMC4439391.

    Article  CAS  PubMed  Google Scholar 

  46. Axilbund JE, Argani P, Kamiyama M, Palmisano E, Raben M, Borges M, et al. Absence of germline BRCA1 mutations in familial pancreatic cancer patients. Cancer Biol Ther. 2009;8(2):131–5. Epub 2008/11/26. PubMed PMID: 19029836; PubMed Central PMCID: PMC2684337.

    Article  CAS  PubMed  Google Scholar 

  47. Thompson D, Easton DF. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94(18):1358–65. PubMed PMID: THOMPSON2002.

    Article  CAS  PubMed  Google Scholar 

  48. Buisson R, Dion-Cote AM, Coulombe Y, Launay H, Cai H, Stasiak AZ, et al. Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination. Nat Struct Mol Biol. 2010;17(10):1247–54. https://doi.org/10.1038/nsmb.1915. PubMed PMID: 20871615; PubMed Central PMCID: PMCPMC4094107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tischkowitz M, Xia B. PALB2/FANCN: recombining cancer and Fanconi anemia. Cancer Res. 2010;70(19):7353–9. https://doi.org/10.1158/0008-5472.CAN-10-1012. PubMed PMID: 20858716; PubMed Central PMCID: PMCPMC2948578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009;324(5924):217. https://doi.org/10.1126/science.1171202. Epub 2009/03/07. PubMed PMID: 19264984; PubMed Central PMCID: PMC2684332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tischkowitz MD, Sabbaghian N, Hamel N, Borgida A, Rosner C, Taherian N, et al. Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology. 2009;137(3):1183–6. https://doi.org/10.1053/j.gastro.2009.06.055. Epub 2009/07/29. S0016-5085(09)01140-8 [pii]. PubMed PMID: 19635604.

    Article  PubMed  Google Scholar 

  52. Slater EP, Langer P, Niemczyk E, Strauch K, Butler J, Habbe N, et al. PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 78(5):490–4. https://doi.org/10.1111/j.1399-0004.2010.01425.x. Epub 2010/04/24. CGE1425 [pii]. PubMed PMID: 20412113.

    Article  CAS  PubMed  Google Scholar 

  53. Casadei S, Norquist BM, Walsh T, Stray S, Mandell JB, Lee MK, et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 2011;71(6):2222–9. https://doi.org/10.1158/0008-5472.CAN-10-3958. PubMed PMID: 21285249; PubMed Central PMCID: PMCPMC3059378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Win AK, Lindor NM, Young JP, Macrae FA, Young GP, Williamson E, et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J Natl Cancer Inst. 2012;104(18):1363–72. https://doi.org/10.1093/jnci/djs351. PubMed PMID: 22933731; PubMed Central PMCID: PMCPMC3529597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kastrinos F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, et al. Risk of pancreatic cancer in families with lynch syndrome. JAMA. 2009;302(16):1790–5. https://doi.org/10.1001/jama.2009.1529. Epub 2009/10/29. 302/16/1790 [pii]. PubMed PMID: 19861671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Raphael KL, Willingham FF. Hereditary pancreatitis: current perspectives. Clin Exp Gastroenterol. 2016;9:197–207. https://doi.org/10.2147/CEG.S84358. PubMed PMID: 27555793; PubMed Central PMCID: PMCPMC4968666.

    Article  PubMed  PubMed Central  Google Scholar 

  57. 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. PubMed PMID: 15017610.

    Article  CAS  PubMed  Google Scholar 

  58. Lowenfels AB, Maisonneuve P, DiMagno EP, Elitsur Y, Gates Jr LK, Perrault J, et al. Hereditary pancreatitis and the risk of pancreatic cancer. International hereditary pancreatitis study group. J Natl Cancer Inst. 1997;89(6):442–6. PubMed PMID: LOWENFELS1997.

    Article  CAS  PubMed  Google Scholar 

  59. Rebours V, Boutron-Ruault MC, Schnee M, Ferec C, Le Marechal C, Hentic O, et al. The natural history of hereditary pancreatitis: a national series. Gut. 2009;58(1):97–103. https://doi.org/10.1136/gut.2008.149179. PubMed PMID: 18755888.

    Article  CAS  PubMed  Google Scholar 

  60. Lowenfels AB, Maisonneuve P, Whitcomb DC, Lerch MM, DiMagno EP. Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA. 2001;286(2):169–70. PubMed PMID: LOWENFELS2001.

    Article  CAS  PubMed  Google Scholar 

  61. McGarrity TJ, Amos CI, Baker MJ. Peutz-Jeghers syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, LJH B, et al., editors. GeneReviews(R). Seattle: University of Washington; 1993.

    Google Scholar 

  62. Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV, et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med. 1987;316(24):1511–4. PubMed PMID: GIARDIELLO1987.

    Article  CAS  PubMed  Google Scholar 

  63. van Lier MG, Wagner A, Mathus-Vliegen EM, Kuipers EJ, Steyerberg EW, van Leerdam ME. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 105(6):1258–64. https://doi.org/10.1038/ajg.2009.725; author reply 65. Epub 2010/01/07. ajg2009725 [pii]. PubMed PMID: 20051941.

  64. Resta N, Pierannunzio D, Lenato GM, Stella A, Capocaccia R, Bagnulo R, et al. Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study. Dig Liver Dis. 2013;45(7):606–11. https://doi.org/10.1016/j.dld.2012.12.018. PubMed PMID: 23415580.

    Article  CAS  PubMed  Google Scholar 

  65. Rayess H, Wang MB, Srivatsan ES. Cellular senescence and tumor suppressor gene p16. Int J Cancer. 2012;130(8):1715–25. https://doi.org/10.1002/ijc.27316. PubMed PMID: 22025288; PubMed Central PMCID: PMCPMC3288293.

    Article  CAS  PubMed  Google Scholar 

  66. Lowe SW, Sherr CJ. Tumor suppression by Ink4a-Arf: progress and puzzles. Curr Opin Genet Dev. 2003;13(1):77–83. PubMed PMID: 12573439.

    Article  CAS  PubMed  Google Scholar 

  67. Wood LD, Hruban RH. Pathology and molecular genetics of pancreatic neoplasms. Cancer J. 2012;18(6):492–501. https://doi.org/10.1097/PPO.0b013e31827459b6. PubMed PMID: 23187835; PubMed Central PMCID: PMCPMC4013751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bado A, Hervatin F, Lewin MJ. Pharmacological evidence for histamine H3 receptor in the control of gastric acid secretion in cats. Am J Phys. 1991;260(4 Pt 1):G631–5. PubMed PMID: 1850206.

    CAS  Google Scholar 

  69. Moskaluk CA, Hruban RH, Kern SE. p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 1997;57(11):2140–3. PubMed PMID: MOSKALUK1997.

    CAS  PubMed  Google Scholar 

  70. Wilentz RE, Geradts J, Maynard R, Offerhaus GJ, Kang M, Goggins M, et al. Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression. Cancer Res. 1998;58(20):4740–4. PubMed PMID: 9788631.

    CAS  PubMed  Google Scholar 

  71. Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006;66(20):9818–28. PubMed PMID: GOLDSTEIN2006.

    Article  CAS  PubMed  Google Scholar 

  72. Zamyatnin AA. Structural classification of endogenous regulatory oligopeptides. Protein Seq Data Anal. 1991;4(1):53–6. PubMed PMID: 1924270.

    CAS  PubMed  Google Scholar 

  73. McWilliams RR, Wieben ED, Rabe KG, Pedersen KS, Wu Y, Sicotte H, et al. Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling. Eur J Hum Genet. 2011;19(4):472–8. https://doi.org/10.1038/ejhg.2010.198. PubMed PMID: 21150883; PubMed Central PMCID: PMCPMC3060321.

    Article  CAS  PubMed  Google Scholar 

  74. Mukherjee B, Delancey JO, Raskin L, Everett J, Jeter J, Begg CB, et al. Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers. J Natl Cancer Inst. 2012;104(12):953–6. https://doi.org/10.1093/jnci/djs221. PubMed PMID: 22534780; PubMed Central PMCID: PMCPMC3379723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Smith AL, Alirezaie N, Connor A, Chan-Seng-Yue M, Grant R, Selander I, et al. Candidate DNA repair susceptibility genes identified by exome sequencing in high-risk pancreatic cancer. Cancer Lett. 2016;370(2):302–12. https://doi.org/10.1016/j.canlet.2015.10.030. PubMed PMID: 26546047.

    Article  CAS  PubMed  Google Scholar 

  76. Witt H, Beer S, Rosendahl J, Chen JM, Chandak GR, Masamune A, et al. Variants in CPA1 are strongly associated with early onset chronic pancreatitis. Nat Genet. 2013;45(10):1216–20. https://doi.org/10.1038/ng.2730. PubMed PMID: 23955596; PubMed Central PMCID: PMCPMC3909499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, et al. Pancreatitis and the risk of pancreatic cancer. International pancreatitis study group. N Engl J Med. 1993;328(20):1433–7. PubMed PMID: LOWENFELS1993.

    Article  CAS  PubMed  Google Scholar 

  78. Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009;41(9):986–90. https://doi.org/10.1038/ng.429. Epub 2009/08/04. PubMed PMID: 19648918; PubMed Central PMCID: PMC2839871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, Jacobs KB, et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010;42(3):224–8. https://doi.org/10.1038/ng.522. Epub 2010/01/27. PubMed PMID: 20101243; PubMed Central PMCID: PMC2853179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, et al. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet. 2014;46(9):994–1000. https://doi.org/10.1038/ng.3052. Epub 2014/08/05. PubMed PMID: 25086665; PubMed Central PMCID: PMC4191666.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Childs EJ, Mocci E, Campa D, Bracci PM, Gallinger S, Goggins M, et al. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nat Genet. 2015;47(8):911–6. https://doi.org/10.1038/ng.3341. PubMed PMID: 26098869; PubMed Central PMCID: PMCPMC4520746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wu C, Miao X, Huang L, Che X, Jiang G, Yu D, et al. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat Genet. 2012;44(1):62–6. https://doi.org/10.1038/ng.1020. PubMed PMID: 22158540.

    Article  CAS  Google Scholar 

  83. Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, et al. International cancer of the pancreas screening (CAPS) consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62(3):339–47. https://doi.org/10.1136/gutjnl-2012-303108. Epub 2012/11/09. PubMed PMID: 23135763; PubMed Central PMCID: PMC3585492.

    Article  PubMed  Google Scholar 

  84. van der Heijden MS, Brody JR, Dezentje DA, Gallmeier E, Cunningham SC, Swartz MJ, et al. In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res. 2005;11(20):7508–15. PubMed PMID: VANDERHEIJDEN2005.

    Article  PubMed  Google Scholar 

  85. Bhalla A, Saif MW. PARP-inhibitors in BRCA-associated pancreatic cancer. JOP. 2014;15(4):340–3. https://doi.org/10.6092/1590-8577/2690. PubMed PMID: 25076338.

    Article  PubMed  Google Scholar 

  86. Villarroel MC, Rajeshkumar NV, Garrido-Laguna I, De Jesus-Acosta A, Jones S, Maitra A, et al. Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. Mol Cancer Ther. 2011;10(1):3–8. https://doi.org/10.1158/1535-7163.MCT-10-0893. Epub 2010/12/08. PubMed PMID: 21135251; PubMed Central PMCID: PMC3307340.

    Article  CAS  PubMed  Google Scholar 

  87. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21. https://doi.org/10.1038/nature03445. PubMed PMID: 15829967.

    Article  CAS  PubMed  Google Scholar 

  88. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913–7. PubMed PMID: 15829966.

    Article  CAS  PubMed  Google Scholar 

  89. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376(9737):235–44. https://doi.org/10.1016/S0140-6736(10)60892-6. PubMed PMID: 20609467.

    Article  CAS  PubMed  Google Scholar 

  90. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361(2):123–34. https://doi.org/10.1056/NEJMoa0900212. PubMed PMID: 19553641.

    Article  CAS  PubMed  Google Scholar 

  91. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20. https://doi.org/10.1056/NEJMoa1500596. PubMed PMID: 26028255; PubMed Central PMCID: PMCPMC4481136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Wilentz RE, Goggins M, Redston M, Marcus VA, Adsay NV, Sohn TA, et al. Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: a newly described and characterized entity. Am J Pathol. 2000;156(5):1641–51. PubMed PMID: WILENTZ2000A.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Nicholas J. Roberts

  2. The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Alison P. Klein

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  1. Nicholas J. Roberts
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  2. Alison P. Klein
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Correspondence to Nicholas J. Roberts .

Editor information

Editors and Affiliations

  1. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    John P. Neoptolemos

  2. Division of Research Department of Surgery and Genomic Sciences and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Raul Urrutia

  3. Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA

    James L. Abbruzzese

  4. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    Markus W. Büchler

Section Editor information

  1. Mayo Clinic Cancer Center, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA

    Raul A. Urrutia

  2. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Markus W. Büchler

  3. Division of Surgery and Oncology, University of Liverpool, Daulby Street, Liverpool, UK

    John Neoptolemos

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Roberts, N.J., Klein, A.P. (2018). Familial Pancreatic Cancer. In: Neoptolemos, J., Urrutia, R., Abbruzzese, J., Büchler, M. (eds) Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7193-0_78

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