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Diagnosis and Management of Hereditary Pancreatic Cancer

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Rare Hereditary Cancers

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 205))

Abstract

Hereditary pancreatic cancer can be diagnosed through family history and/or a personal history of pancreatitis or clinical features suggesting one of the known pancreatic cancer predisposition syndromes. This chapter describes the currently known hereditary pancreatic cancer predisposition syndromes, including Peutz–Jeghers syndrome, familial atypical multiple mole melanoma, hereditary breast and ovarian cancer, Li–Fraumeni syndrome, hereditary non-polyposis colon cancer and familial adenomatous polyposis. Strategies for genetic testing for hereditary pancreatic cancer and the appropriate options for surveillance and cancer risk reduction are discussed. Finally, ongoing research and future directions in the diagnosis and management of hereditary pancreatic cancer will be considered.

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References

  • (AIHW) A. I. O. H. A. W. (2014) Australian cancer incidence and mortality (ACIM) books: pancreatic cancer. AIHW, Canberra. http://www.aihw.gov.au/acim-books%3E

  • Al-Sukhni W, Borgida A, Rothenmund H, Holter S, Semotiuk K, Grant R et al (2012). Screening for pancreatic cancer in a high-risk cohort: an eight-year experience. J Gastrointest Surg: official J Soc Surg Aliment Tract 16(4):771–783

    Google Scholar 

  • Agarwal B, Correa AM, Ho L (2008) Survival in pancreatic carcinoma based on tumor size. Pancreas 36:e15–e20

    Article  PubMed  Google Scholar 

  • Alexandrov LB, Nik-Zainal S, Wedge DC, Campbell PJ, Stratton MR (2013) Deciphering signatures of mutational processes operative in human cancer. Cell Rep 3:246–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson M, Zolotarevsky E, Cooper K et al (2012) Alcohol and tobacco lower the age of presentation in sporadic pancreatic cancer in a dose-dependent manner: a multicenter study. Am J Gastroenterol 107:1730–1739. doi:10.1038/ajg.2012.288 Epub 2012 Aug 28

    Article  PubMed  PubMed Central  Google Scholar 

  • Arslan AA, Helzlsouer KJ, Kooperberg C et al (2010) Anthropometric measures, body mass index, and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Arch Intern Med 170:791–802

    Article  PubMed  PubMed Central  Google Scholar 

  • Axilbund JE, Argani P, Kamiyama M et al (2009) Absence of germline BRCA1 mutations in familial pancreatic cancer patients. Cancer Biol Ther 8:131–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barratt A, Mannes P, Irwig L, Trevena L, Craig J, Rychetnik L (2002) Cancer screening. J Epidemiol Commun Health 56:899–902

    Article  CAS  Google Scholar 

  • Barton J, Schnelldorfer T, Lohse C et al (2011) Patterns of pancreatic resection differ between patients with familial and sporadic pancreatic cancer. J Gastrointest Surg 15:836–842. doi:10.1007/s11605-011-1417-x Epub 2011 Feb 26

    Article  PubMed  PubMed Central  Google Scholar 

  • Bartsch D, Kress R, Sina-Frey M et al (2004) Prevalence of familial pancreatic cancer in Germany. Int J Cancer 110:902–906

    Article  CAS  PubMed  Google Scholar 

  • Bartsch D, Gress T, Langer P (2012) Familial pancreatic cancer–current knowledge. Nat Rev Gastroenterol Hepatol 9:445–453. doi:10.1038/nrgastro.2012.111 Epub 2012 Jun 5

    Article  CAS  PubMed  Google Scholar 

  • Beggs AD, Latchford AR, Vasen HFA et al (2010) Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut 59:975–986

    Article  CAS  PubMed  Google Scholar 

  • Berthelemy P, Bouisson M, Escourrou J et al (1995) Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer. Ann Intern Med 123:188–191

    Article  CAS  PubMed  Google Scholar 

  • Birch JM, Alston RD, McNally R et al (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20:4621–4628

    Article  CAS  PubMed  Google Scholar 

  • Bosetti C, Lucenteforte E, Silverman DT et al (2012) Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 23:1880–1888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brand RE, Lerch MM, Rubinstein WS et al (2007) Advances in counselling and surveillance of patients at risk for pancreatic cancer. Gut 56:1460–1469

    Article  PubMed  PubMed Central  Google Scholar 

  • Breast Cancer Linkage Consortimu (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91:1310–1316

    Article  Google Scholar 

  • Brentnall T, Bronner M, Byrd D, Haggitt R, Kimmey M (1999). Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 131(4):247–255

    Google Scholar 

  • Brentnall TA, Lai LA, Coleman J et al (2012) Arousal of cancer-associated stroma: overexpression of palladin activates fibroblasts to promote tumor invasion. PLoS ONE 7:e30219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brose MS, Rebbeck TR, Calzone KA et al (2002) Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94:1365–1372

    Article  CAS  PubMed  Google Scholar 

  • Brune K, Lau B, Palmisano E, Canto M, Goggins M, Hruban R et al (2010). Importance of age of onset in pancreatic cancer kindreds. J Natl Cancer Inst 102(2):119–26. doi: 10.1093/jnci/djp466. Epub 2010 Jan 12

    Google Scholar 

  • Canto M, Goggins M, Hruban R, Petersen G, Giardiello F, Yeo C et al (2006). Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 4(6):766–781; quiz 665. Epub 2006 May 6

    Google Scholar 

  • Canto M, Goggins M, Yeo C, Griffin C, Axilbund J, Brune K, et al (2004). Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol 2(7):606–621

    Google Scholar 

  • Canto M, Hruban R, Fishman E, Kamel I, Schulick R, Zhang Z et al (2012). Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology 142(4):796–804; quiz e14-5. doi: 10.1053/j.gastro.2012.01.005. Epub Jan 12.

    Google Scholar 

  • Canto MI, Harinck F, Hruban RH et al (2013a) International Cancer of the Pancreas Screening (CAPS) consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 62:339–347

    Article  PubMed  PubMed Central  Google Scholar 

  • Canto MI, Harinck F, Hruban RH et al (2013b) International Cancer of the Pancreas Screening (CAPS) consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 62:339–347

    Article  PubMed  PubMed Central  Google Scholar 

  • Carnevale J, Ashworth A (2015) Assessing the Significance of BRCA1 and BRCA2 mutations in pancreatic cancer. J Clin Oncol JCO 2015 OCT 1; 33(28):3080–3081

    Google Scholar 

  • Chetty R, Salahshor S, Bapat B et al (2005) Intraductal papillary mucinous neoplasm of the pancreas in a patient with attenuated familial adenomatous polyposis. J Clin Pathol 58:97–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cote M, Schenk M, Schwartz A et al (2007) Risk of other cancers in individuals with a family history of pancreas cancer. J Gastrointest Cancer. 38:119–126. doi:10.1007/s12029-008-9022-2

    Article  PubMed  PubMed Central  Google Scholar 

  • Cotterchio M, Lowcock E, Hudson TJ et al (2014) Association between allergies and risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev

    Google Scholar 

  • Couch F, Johnson M, Rabe K et al (2007a) The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 16:342–346

    Article  CAS  PubMed  Google Scholar 

  • Couch FJ, Johnson MR, Rabe KG et al (2007b) The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 16:342–346

    Article  CAS  PubMed  Google Scholar 

  • Couch FJ, Hart SN, Sharma P et al (2014) Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol

    Google Scholar 

  • del Chiaro M, Zerbi A, Capurso G et al (2010) Familial pancreatic cancer in Italy. Risk assessment, screening programs and clinical approach: a position paper from the Italian Registry. Dig Liver Dis 42:597–605

    Article  PubMed  Google Scholar 

  • Duell EJ, Lucenteforte E, Olson SH et al (2012) Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 23:2964–2970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eldridge RC, Gapstur SM, Newton CC et al (2011) Jewish ethnicity and pancreatic cancer mortality in a large U.S. Cohort Cancer Epidemiol Biomarkers Prev 20:691–698

    Article  PubMed  Google Scholar 

  • Ferlay JSI, Ervik M, Dikshit R et al (2013) Globocan 2012 v1.0, cancer incidence and mortality worldwide: IARC cancerbase no. 11 [Internet]. International Agency for Research on Cancer, Lyon, France. Available from: http://globocan.iarc.fr. Accessed on 14 Dec 2015

  • Ferrone CR, Levine DA, Tang LH et al (2009) BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J Clin Oncol 27:433–438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franko J, Hugec V, Lopes T, Goldman C (2013) Survival Among Pancreaticoduodenectomy Patients Treated for Pancreatic Head Cancer <1 or 2 cm. Ann Surg Oncol 20:357–361

    Article  PubMed  Google Scholar 

  • Garber JE, Goldstein AM, Kantor AF et al (1991) Follow-up study of twenty-four families with Li-Fraumeni syndrome. Cancer Res 51:6094–6097

    CAS  PubMed  Google Scholar 

  • Genkinger JM, Spiegelman D, Anderson KE et al (2009) Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiol Biomarkers Prev 18:765–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghadirian P, Boyle P, Simard A et al (1991) Reported family aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal. Can Int J Pancreatol 10:183–196

    CAS  PubMed  Google Scholar 

  • Ghiorzo P, Fornarini G, Sciallero S et al (2012) CDKN2A is the main susceptibility gene in Italian pancreatic cancer families. J Med Genet 49:164–170

    Article  CAS  PubMed  Google Scholar 

  • Giardiello FM, Offerhaus GJ, Lee DH, Krush AJ, Tersmette AC, Booker SV, Kelley NC, Hamilton SR (1993) Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut 34:1394–1396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goggins M (2011) Markers of pancreatic cancer: working toward early detection. Clin Cancer Res 17:635–637

    Article  PubMed  PubMed Central  Google Scholar 

  • Goggins M, Schutte M, Lu J et al (1996) Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 56:5360–5364

    CAS  PubMed  Google Scholar 

  • Gold DV, Goggins M, Modrak DE et al (2010) Detection of early-stage pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev 19:2786–2794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grant RC, Selander I, Connor AA et al (2014) Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer. Gastroenterology

    Google Scholar 

  • Grimes DA, Schulz KF (2002) Uses and abuses of screening tests. Lancet 359:881–884

    Article  PubMed  Google Scholar 

  • Groden J, Thliveris A, Samowitz W et al (1991) Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66:589–600

    Article  CAS  PubMed  Google Scholar 

  • Hahn S, Greenhalf B, Ellis I et al (2003) BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 95:214–221

    Article  CAS  PubMed  Google Scholar 

  • Hampel H, Bennett RL, Buchanan A et al (2014) A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med

    Google Scholar 

  • Hearle N, Schumacher V, Menko FH et al (2006) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12:3209–3215

    Article  CAS  PubMed  Google Scholar 

  • Hemminki K, Li X (2003) Familial and second primary pancreatic cancers: a nationwide epidemiologic study from Sweden. Int J Cancer 103:525–530

    Article  CAS  PubMed  Google Scholar 

  • Holter S, Borgida A, Dodd A et al (2015) Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma. J Clin Oncol

    Google Scholar 

  • Howes N, Lerch MM, Greenhalf W et al (2004) Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol 2:252–261

    Article  CAS  PubMed  Google Scholar 

  • Hruban RH, Goggins M, Parsons J, Kern SE (2000) Progression model for pancreatic cancer. Clin Cancer Res 6:2969–2972

    CAS  PubMed  Google Scholar 

  • Hruban RH, Takaori K, Klimstra DS et al (2004) An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 28:977–987

    Article  PubMed  Google Scholar 

  • Hruban RH, Maitra A, Goggins M (2008) Update on pancreatic intraepithelial neoplasia. Int J Clin Experimen Pathol 1:306

    CAS  Google Scholar 

  • Hruban R, Canto M, Goggins M, Schulick R, Klein A (2010) Update on familial pancreatic cancer. Adv Surg 44:293–311

    Article  PubMed  PubMed Central  Google Scholar 

  • Hudson TJ, Anderson W, Artez A et al (2010) International network of cancer genome projects. Nature 464:993–998

    Article  CAS  PubMed  Google Scholar 

  • Iqbal J, Ragone A, Lubinski J et al (2012) The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer 107:2005–2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jabbar KS, Verbeke C, Hyltander AG et al (2014) Proteomic mucin profiling for the identification of cystic precursors of pancreatic cancer J National Cancer Institute 106

    Google Scholar 

  • Jones S, Hruban RH, Kamiyama M et al (2009) Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324:217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kastrinos F, Mukherjee B, Tayob N et al (2009) Risk of pancreatic cancer in families with Lynch syndrome. JAMA 302:1790–1795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaufman B, Shapira-Frommer R, Schmutzler RK et al (2015) Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. J Clin Oncol 33:244–250

    Article  CAS  PubMed  Google Scholar 

  • Kimmey M, Bronner M, Byrd D, Brentnall T (2002). Screening and surveillance for hereditary pancreatic cancer. Gastrointest Endosc 56(4 Suppl):S82–6

    Google Scholar 

  • Klein A (2013a) Identifying people at a high risk of developing pancreatic cancer. Nat Rev Cancer 13:66–74. doi:10.1038/nrc3420 Epub 2012 Dec 6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klein AP (2013b) Identifying people at a high risk of developing pancreatic cancer. Nat Rev Cancer 13:66–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klein AP, Beaty TH, Bailey-Wilson JE et al (2002) Evidence for a major gene influencing risk of pancreatic cancer. Genet Epidemiol 23:133–149

    Article  PubMed  Google Scholar 

  • Klein AP, Brune KA, Petersen GM et al (2004) Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res 64:2634–2638

    Article  CAS  PubMed  Google Scholar 

  • Koopmann J, Rosenzweig CNW, Zhang Z et al (2006) Serum markers in patients with resectable pancreatic adenocarcinoma: macrophage inhibitory cytokine 1 versus CA19-9. Clin Cancer Res 12:442–446

    Article  CAS  PubMed  Google Scholar 

  • Korsse SE, Harinck F, van Lier MGF et al (2013) Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance. J Med Genet 50:59–64

    Article  CAS  PubMed  Google Scholar 

  • Kuiper RP, Vissers LE, Venkatachalam R et al (2011) Recurrence and variability of germline EPCAM deletions in Lynch syndrome. Hum Mutat 32:407–414

    Article  CAS  PubMed  Google Scholar 

  • Lal G, Liu G, Schmocker B et al (2000) Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1, and BRCA2 mutations. Cancer Res 60:409–416

    CAS  PubMed  Google Scholar 

  • Langer P, Kann PH, Fendrich V, Habbe N, Schneider M, Sina M et al (2009). Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer. Gut 58(10):1410–1418

    Google Scholar 

  • Lennon AM, Wolfgang CL, Canto MI et al (2014) The early detection of pancreatic cancer: what will it take to diagnose and treat curable pancreatic neoplasia? Cancer Res 74:3381–3389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leonardi G, Marchi S, Falconi M et al (2012) “PancPro” as a tool for selecting families eligible for pancreatic cancer screening: an Italian study of incident cases. Dig Liver Dis 44:585–588

    Article  PubMed  Google Scholar 

  • Li FP, Fraumeni JJF (1969) Soft-tissue sarcomas, breast cancer, and other neoplasmsa familial syndrome? Ann Intern Med 71:747–752

    Article  CAS  PubMed  Google Scholar 

  • Li FP, Fraumeni JF Jr., Mulvihill JJ et al (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48:5358–5362

    Google Scholar 

  • Li D, Tang H, Hassan MM et al (2011) Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies. Cancer Causes Control 22:189–197

    Article  CAS  PubMed  Google Scholar 

  • Ligtenberg MJ, Kuiper RP, Chan TL et al (2009) Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3’ exons of TACSTD1. Nat Genet 41:112–117

    Article  CAS  PubMed  Google Scholar 

  • Liu R, Chen X, Du Y et al (2012) Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem 58:610–618

    Article  CAS  PubMed  Google Scholar 

  • Lowenfels AB, Maisonneuve P, Dimagno EP et al (1997) Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 89:442–446

    Article  CAS  PubMed  Google Scholar 

  • Lowenfels AB, Maisonneuve P, Whitcomb DC et al (2001) Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA 286:169–170

    Article  CAS  PubMed  Google Scholar 

  • Lu KH, Wood ME, Daniels M et al (2014) American society of clinical oncology expert statement: collection and use of a cancer family history for oncology providers. J Clin Oncol 32:833–840

    Article  PubMed  PubMed Central  Google Scholar 

  • Lucas AL, Shakya R, Lipsyc MD et al (2013) High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions. Clin Cancer Res 19:3396–3403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ludwig E, Olson SH, Bayuga S, Simon J, Schattner MA, Gerdes H et al (2011). Feasibility and yield of screening in relatives from familial pancreatic cancer families. Am J Gastroenterol 106(5):946–954

    Google Scholar 

  • Lynch H, Fitzsimmons M, Smyrk T et al (1990) Familial pancreatic cancer: clinicopathologic study of 18 nuclear families. Am J Gastroenterol 85:54–60

    CAS  PubMed  Google Scholar 

  • Macarthur DG, Manolio TA, Dimmock DP et al (2014) Guidelines for investigating causality of sequence variants in human disease. Nature 508:469–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manolio TA, Collins FS, Cox NJ et al (2009) Finding the missing heritability of complex diseases. Nature 461:747–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McFaul C, Greenhalf W, Earl J et al (2006) Anticipation in familial pancreatic cancer. Gut. 55:252–258 Epub 2005 Jun 21

    CAS  PubMed  Google Scholar 

  • McGarrity TJ, Amos C, Frazier ML et al (2013) Peutz-Jeghers Syndrome. 2001 Feb 23 (Updated 2013 Jul 25). In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews® [Internet]. University of Washington, Seattle (WA), 1993–2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1266/

  • Moran A, O’Hara C, Khan S et al (2012) Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam Cancer 11:235–242. doi:10.1007/s10689-011-9506-2

    Article  CAS  PubMed  Google Scholar 

  • Mulcahy HE, Lyautey J, Lederrey C et al (1998) A prospective study of K-ras mutations in the plasma of pancreatic cancer patients. Clin Cancer Res 4:271–275

    CAS  PubMed  Google Scholar 

  • Murphy KM, Brune KA, Griffin C et al (2002) Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17 %. Cancer Res 62:3789–3793

    CAS  PubMed  Google Scholar 

  • National Comprehensive Cancer Network guidelines for prevention, detection and risk reduction. Genetic/familial high-risk assessment: Breast and ovarian version 2.2015. www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 15th December 2015

  • Olson S, Kurtz R (2013) Epidemiology of pancreatic cancer and the role of family history. J Surg Oncol 107:1–7. doi:10.1002/jso.23149 Epub 2012 May 15

    Article  PubMed  PubMed Central  Google Scholar 

  • Ozcelik H, Schmocker B, di Nicola N et al (1997) Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients. Nat Genet 16:17–18

    Article  CAS  PubMed  Google Scholar 

  • Petersen GM, de Andrade M, Goggins M et al (2006) Pancreatic cancer genetic epidemiology consortium. Cancer Epidemiol Biomarkers Prev 15:704–710

    Article  PubMed  Google Scholar 

  • Pogue-Geile KL, Chen R, Bronner MP et al (2006) Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PLoS Med 3:e516

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Poley JW, Kluijt I, Gouma DJ, Harinck F, Wagner A, Aalfs C et al (2009). The Yield of First-Time Endoscopic Ultrasonography in Screening Individuals at a High Risk of Developing Pancreatic Cancer. Am J Gastroenterol 104(9):2175–2181

    Google Scholar 

  • Raimondi S, Maisonneuve P, Lowenfels A (2009) Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol. 6:699–708. doi:10.1038/nrgastro.2009.177 Epub 2009 Oct 6

    Article  PubMed  Google Scholar 

  • Rebours V, Boutron-Ruault MC, Schnee M et al (2009) The natural history of hereditary pancreatitis: a national series. Gut 58:97–103

    Article  CAS  PubMed  Google Scholar 

  • Risch HA, McLaughlin JR, Cole DE et al (2006) Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst 98:1694–1706

    Article  CAS  PubMed  Google Scholar 

  • Roberts N, Jiao Y, Yu J et al (2012a) ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov 2:41–46. doi:10.1158/2159-8290.CD-11-0194 Epub 2011 Dec 29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts NJ, Jiao Y, Yu J et al (2012b) ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov 2:41–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruijs MW, Verhoef S, Rookus MA et al (2010) TP53 germline mutation testing in 180 families suspected of Li–Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet 47:421–428

    Article  CAS  PubMed  Google Scholar 

  • Rutter JL, Bromley CM, Goldstein AM et al (2004) Heterogeneity of risk for melanoma and pancreatic and digestive malignancies. Cancer 101:2809–2816

    Article  PubMed  Google Scholar 

  • Ryan DP, Hong TS, Bardeesy N (2014) Pancreatic adenocarcinoma. N Engl J Med 371:1039–1049

    Article  CAS  PubMed  Google Scholar 

  • Schneider R, Slater E, Sina M et al (2011a) German national case collection for familial pancreatic cancer (FaPaCa): ten years experience. Fam Cancer 10:323–330. doi:10.1007/s10689-010-9414-x

    Article  PubMed  Google Scholar 

  • Schneider R, Slater EP, Sina M et al (2011b) German national case collection for familial pancreatic cancer (FaPaCa): ten years experience. Fam Cancer 10:323–330

    Article  PubMed  Google Scholar 

  • Shi C, Hruban RH, Klein AP (2009) Familial pancreatic cancer. Arch Pathol Lab Med 133:365–374

    PubMed  Google Scholar 

  • Skudra S, Staka A, Pukitis A et al (2007) Association of genetic variants with pancreatic cancer. Cancer Genet Cytogenet 179:76–78

    Article  CAS  PubMed  Google Scholar 

  • Stadler ZK, Schrader KA, Vijai J, Robson ME, Offit K (2014) Cancer genomics and inherited risk. J Clin Oncol 32:687–698

    Article  CAS  PubMed  Google Scholar 

  • Steinberg W (1990) The clinical utility of the CA 19-9 tumor-associated antigen. Am J Gastroenterol 85:350–355

    CAS  PubMed  Google Scholar 

  • Syngal S, Brand RE, Church JM et al (2015) ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 110:223–262

    Article  PubMed  PubMed Central  Google Scholar 

  • Tersmette A, Petersen G, Offerhaus G et al (2001) Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 7:738–744

    CAS  PubMed  Google Scholar 

  • The Cancer Genome Atlas Network (2012). Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337

    Google Scholar 

  • Thompson D, Easton D (2001) Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 68:410–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tischkowitz MD, Sabbaghian N, Hamel N et al (2009) Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology 137:1183–1186

    Article  PubMed  PubMed Central  Google Scholar 

  • Vasen HFA, Gruis NA, Frants RR et al (2000) Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer 87:809–811

    Article  CAS  PubMed  Google Scholar 

  • Vasen HFA, van der Meulen–de Jong AE, de vos tot Nederveen Cappel WH, Oliveira J (2009) GROUP, O. B. O. T. E. G. W. 2009 Familial colorectal cancer risk: ESMO Clinical Recommendations. Annals of Oncology 20:iv51–iv53

    Google Scholar 

  • Verna EC, Hwang C, Stevens PD, Rotterdam H, Stavropoulos SN, Sy CD et al (2010). Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics. Clinical cancer research 16(20):5028–5037

    Google Scholar 

  • Vasen HF, Wasser M, van Mil A, Tollenaar RA, Konstantinovski M, Gruis NA et al (2011). Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation. Gastroenterology 140(3):850–856

    Google Scholar 

  • Waddell N, Pajic M, Patch A-M et al (2015) Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518:495–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walsh T, Casadei S, Lee MK et al (2011) Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci 108:18032–18037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang W, Chen S, Brune KA et al (2007) PancPRO: risk assessment for individuals with a family history of pancreatic cancer. J Clin Oncol 25:1417–1422

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang L, Brune K, Visvanathan K et al (2009a) Elevated cancer mortality in the relatives of patients with pancreatic cancer. Cancer Epidemiol Biomarkers Prev 18:2829–2834. doi:10.1158/1055-9965.EPI-09-0557 Epub 2009 Oct 20

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang L, Brune KA, Visvanathan K et al (2009b) Elevated cancer mortality in the relatives of patients with pancreatic cancer. Cancer Epidemiol Biomark Prev 18:2829–2834

    Article  Google Scholar 

  • Whitcomb DC, Gorry MC, Preston RA et al (1996) Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 14:141–145

    Article  CAS  PubMed  Google Scholar 

  • Whitcomb DC, Shelton C, Brand RE (2015) Genetics and genetic testing in pancreatic cancer. Gastroenterology

    Google Scholar 

  • Yachida S, Jones S, Bozic I et al (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467:1114–1117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhen DB, Rabe KG, Gallinger S et al (2014) BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. Genet Med

    Google Scholar 

  • Zogopoulos G, Rothenmund H, Eppel A et al (2007) The P239S palladin variant does not account for a significant fraction of hereditary or early onset pancreas cancer. Hum Genet 121:635–637

    Article  PubMed  Google Scholar 

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Correspondence to Jeremy L. Humphris .

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Humphris, J.L., Biankin, A.V. (2016). Diagnosis and Management of Hereditary Pancreatic Cancer. In: Pichert, G., Jacobs, C. (eds) Rare Hereditary Cancers. Recent Results in Cancer Research, vol 205. Springer, Cham. https://doi.org/10.1007/978-3-319-29998-3_5

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