Familial Cancer

, Volume 10, Issue 2, pp 323–330 | Cite as

German national case collection for familial pancreatic cancer (FaPaCa): ten years experience

  • Ralph Schneider
  • Emily P. Slater
  • Mercede Sina
  • Nils Habbe
  • Volker Fendrich
  • Elvira Matthäi
  • Peter LangerEmail author
  • Detlef K. Bartsch


Familial pancreatic cancer (FPC) is a rare hereditary tumor syndrome. The 10-years experience of the national case collection for familial pancreatic cancer of Germany (FaPaCa) is reported. Since 1999 FaPaCa has collected families with at least two first-degree relatives with confirmed pancreatic cancer (PC), who did not fulfill the criteria of other hereditary tumor syndromes. Histopathological verification of tumor diagnoses, and genetic counseling were prerequisites for enrollment of families in FaPaCa. 94 of 452 evaluated families fulfilled the criteria for partaking in FaPaCa. PC represented the sole tumor entity in 38 (40%) families. In 56 families additional tumor types occurred, including breast cancer (n = 28), colon cancer (n = 20) and lung cancer (n = 11). In 70 (74%) families the pattern of inheritance was consistent with an autosomal dominant trait. Compared to the preceding generation, a younger age of onset was observed in the offspring of PC patients (median: 57 vs. 69 years), indicating anticipation. Mutation analyses of BRCA2, PALB2, CDKN2a, RNASEL, STK11, NOD2, CHEK2 and PALLD, revealed deleterious causative germline mutations of BRCA2 and PALB2 in 2 of 70 (3%) and 2 of 41 (4.9%) German FPC families, respectively. Prospective PC screening with EUS, MRI and MRCP detected precancerous lesions (IPMN, multifocal PanIN2/3) or carcinoma in 5.5% (4 of 72) to 12.5% (9 of 72) of individuals at risk, depending on histological verification. Appropriate inclusion of families at high risk for PC in registries, such as FaPaCa, provides a unique and excellent tool to gain clinical and genetic knowledge of FPC. Focused research projects can be conducted most efficiently, when data of different FPC registries are combined.


Familial pancreatic cancer Genetic susceptibility Screening Hereditary tumor syndrome 



We are grateful to all FPC families for participating in the registry. This study was supported by grants 70-2362-Ba2, 70-2828-Ba3 and 103709 of the Deutsche Krebshilfe.


  1. 1.
    Cooperman AM (2001) Pancreatic cancer: the bigger picture. Surg Clin North Am 81:557–574PubMedCrossRefGoogle Scholar
  2. 2.
    Cleary SP, Gryfe R, Guindi M et al (2004) Prognostic factors in resected pancreatic adenocarcinoma: analysis of actual 5-year survivors. J Am Coll Surg 198:722–731PubMedCrossRefGoogle Scholar
  3. 3.
    Hruban RH, Petersen GM, Ha PK et al (1998) Genetics of pancreatic cancer. From genes to families. Surg Oncol Clin N Am 7:1–23PubMedGoogle Scholar
  4. 4.
    Lynch HT, Brand RE, Deters CA et al (2001) Hereditary pancreatic cancer. Pancreatology 1:466–471PubMedCrossRefGoogle Scholar
  5. 5.
    Applebaum SE, Kant JA, Whitcomb DC et al (2000) Genetic testing. Counseling, laboratory, and regulatory issues and the EUROPAC protocol for ethical research in multicenter studies of inherited pancreatic diseases. Med Clin North Am 84:575–588 viiiPubMedCrossRefGoogle Scholar
  6. 6.
    Ehrenthal D, Haeger L, Griffin T et al (1987) Familial pancreatic adenocarcinoma in three generations. A case report and a review of the literature. Cancer 59:1661–1664PubMedCrossRefGoogle Scholar
  7. 7.
    MacDermott RP, Kramer P (1973) Adenocarcinoma of the pancreas in four siblings. Gastroenterology 65:137–139PubMedGoogle Scholar
  8. 8.
    Reimer RR, Fraumeni JF Jr, Ozols RF et al (1977) Pancreatic cancer in father and son. Lancet 1:911PubMedCrossRefGoogle Scholar
  9. 9.
    Lynch HT, Lanspa SJ, Fitzgibbons RJ Jr et al (1989) Familial pancreatic cancer (part 1): genetic pathology review. Nebr Med J 74:109–112PubMedGoogle Scholar
  10. 10.
    Bartsch DK, Sina-Frey M, Ziegler A et al (2001) Update of familial pancreatic cancer in Germany. Pancreatology 1:510–516PubMedCrossRefGoogle Scholar
  11. 11.
    Tersmette AC, Petersen GM, Offerhaus GJ et al (2001) Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 7:738–744PubMedGoogle Scholar
  12. 12.
    Hruban RH, Petersen GM, Goggins M et al (1999) Familial pancreatic cancer. Ann Oncol 10(Suppl 4):69–73PubMedCrossRefGoogle Scholar
  13. 13.
    Bartsch DK, Kress R, Sina-Frey M et al (2004) Prevalence of familial pancreatic cancer in Germany. Int J Cancer 110:902–906PubMedCrossRefGoogle Scholar
  14. 14.
    Hemminki K, Li X (2003) Familial and second primary pancreatic cancers: a nationwide epidemiologic study from Sweden. Int J Cancer 103:525–530PubMedCrossRefGoogle Scholar
  15. 15.
    Hahn SA, Greenhalf B, Ellis I et al (2003) BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 95:214–221PubMedCrossRefGoogle Scholar
  16. 16.
    Bartsch DK, Fendrich V, Slater EP et al (2005) RNASEL germline variants are associated with pancreatic cancer. Int J Cancer 117:718–722PubMedCrossRefGoogle Scholar
  17. 17.
    Bartsch DK, Krysewski K, Sina-Frey M et al (2006) Low frequency of CHEK2 mutations in familial pancreatic cancer. Fam Cancer 5:305–308PubMedCrossRefGoogle Scholar
  18. 18.
    Bartsch DK, Sina-Frey M, Lang S et al (2002) CDKN2A germline mutations in familial pancreatic cancer. Ann Surg 236:730–737PubMedCrossRefGoogle Scholar
  19. 19.
    Grutzmann R, McFaul C, Bartsch DK et al (2004) No evidence for germline mutations of the LKB1/STK11 gene in familial pancreatic carcinoma. Cancer Lett 214:63–68PubMedCrossRefGoogle Scholar
  20. 20.
    Nej K, Bartsch DK, Sina-Frey M et al (2004) The NOD23020insC mutation and the risk of familial pancreatic cancer? Hered Cancer Clin Pract 2:149–150PubMedCrossRefGoogle Scholar
  21. 21.
    Slater E, Amrillaeva V, Fendrich V et al (2007) Palladin mutation causes familial pancreatic cancer: absence in European families. PLoS Med 4:e164PubMedCrossRefGoogle Scholar
  22. 22.
    Slater EP, Langer P, Habbe N et al. (2010) Prevalence of PALB2 mutations in familial pancreatic cancer. Clin Genet (in press)Google Scholar
  23. 23.
    Bartsch DK, Langer P, Habbe N et al. (2009) Clinical and genetic analysis of 18 pancreatic carcinoma/melanoma-prone families. Clin Genet 77:333–341PubMedCrossRefGoogle Scholar
  24. 24.
    McFaul CD, Greenhalf W, Earl J et al (2006) Anticipation in familial pancreatic cancer. Gut 55:252–258PubMedCrossRefGoogle Scholar
  25. 25.
    Slater EP, Langer P, Fendrich V et al. (2010) Prevalence of BRCA2 and CDKN2a mutations in German familial pancreatic cancer families. Fam Cancer 9:335–343PubMedCrossRefGoogle Scholar
  26. 26.
    Langer P, Kann PH, Fendrich V et al (2009) Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer. Gut 58:1410–1418PubMedCrossRefGoogle Scholar
  27. 27.
    Lynch HT, Fusaro L, Smyrk TC et al (1995) Medical genetic study of eight pancreatic cancer-prone families. Cancer Invest 13:141–149PubMedCrossRefGoogle Scholar
  28. 28.
    Greenhalf W, Malats N, Nilsson M et al (2008) International registries of families at high risk of pancreatic cancer. Pancreatology 8:558–565PubMedCrossRefGoogle Scholar
  29. 29.
    Schuz J, Schon D, Batzler W et al (2000) Cancer registration in Germany: current status, perspectives and trends in cancer incidence 1973–93. J Epidemiol Biostat 5:99–107PubMedGoogle Scholar
  30. 30.
    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 62:3789–3793PubMedGoogle Scholar
  31. 31.
    Couch FJ, Johnson MR, Rabe KG et al (2007) The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomark Prev 16:342–346CrossRefGoogle Scholar
  32. 32.
    Jones S, Hruban RH, Kamiyama M et al (2009) Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324:217PubMedCrossRefGoogle Scholar
  33. 33.
    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:e516PubMedCrossRefGoogle Scholar
  34. 34.
    Earl J, Yan L, Vitone LJ et al (2006) Evaluation of the 4q32–34 locus in European familial pancreatic cancer. Cancer Epidemiol Biomark Prev 15:1948–1955CrossRefGoogle Scholar
  35. 35.
    Brand RE (2009) Screening for familial pancreatic cancer: is doing something better than doing nothing? Gut 58:1321–1322PubMedCrossRefGoogle Scholar
  36. 36.
    Canto MI, Goggins M, Yeo CJ et al (2004) Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol 2:606–621PubMedCrossRefGoogle Scholar
  37. 37.
    Canto MI, Goggins M, Hruban RH et al (2006) Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 4:766–781PubMedCrossRefGoogle Scholar
  38. 38.
    Poley JW, Kluijt I, Gouma DJ et al (2009) The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. Am J Gastroenterol 104:2175–2181PubMedCrossRefGoogle Scholar
  39. 39.
    Brentnall TA (2005) Management strategies for patients with hereditary pancreatic cancer. Curr Treat Options Oncol 6:437–445PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Ralph Schneider
    • 1
  • Emily P. Slater
    • 1
  • Mercede Sina
    • 2
  • Nils Habbe
    • 1
  • Volker Fendrich
    • 1
  • Elvira Matthäi
    • 1
  • Peter Langer
    • 1
    Email author
  • Detlef K. Bartsch
    • 1
  1. 1.Department of Visceral, Thoracic and Vascular SurgeryPhilipps University MarburgMarburgGermany
  2. 2.Institute of Clinical GeneticsPhilipps University MarburgMarburgGermany

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