Familial Cancer

, Volume 10, Issue 2, pp 391–396

Familial gastric cancer: update for practice management

  • Giovanni Corso
  • Daniele Marrelli
  • Franco Roviello
Article

Abstract

About 90% of gastric carcinoma presents a sporadic setting and only 10% shows a familial cluster; among this group, 1–3% are considered as hereditary syndromes, with a clear genetic pathway. The most important genetic mechanisms are associated with CDH1 germline mutations, causing the hereditary diffuse gastric cancer syndrome. Other inherited predispositions with gastric carcinoma are the hereditary nonpolyposis colorectal cancer, Li-Fraumeni and Peutz-Jeghers syndromes. In this brief update, we described these principal hereditary syndromes offering a simple management to physicians where are these diseases diagnosed.

Keywords

E-cadherin Mismatch repair genes TP53 STK11 

References

  1. 1.
    Lynch HT, Lynch JF (2002) Cancer family history and genetic testing: are malpractice adjudications waiting to happen? Am J Gastroenterol 97:518–520PubMedCrossRefGoogle Scholar
  2. 2.
    Guilford P, Hopkins J, Harraway J et al (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392:402–405PubMedCrossRefGoogle Scholar
  3. 3.
    Caldas C, Carneiro F, Lynch HT et al (1999) Familial gastric cancer: overview and guidelines for management. J Med Genet 36:873–880PubMedGoogle Scholar
  4. 4.
    Oliveira C, Carneiro F, Seruca R (2009) Hereditary gastric cancer. Best Pract Res Clin Gastroenterol 23:147–157PubMedCrossRefGoogle Scholar
  5. 5.
    Pedrazzani C, Corso G, Velho S et al (2009) Evidence of tumor microsatellite instability in gastric cancer with familial aggregation. Fam Cancer 8:215–220PubMedCrossRefGoogle Scholar
  6. 6.
    Palli D, Russo A, Ottini L et al (2001) Red meat, family history, and increased risk of gastric cancer with microsatellite instability. Cancer Res 61:5415–5419PubMedGoogle Scholar
  7. 7.
    Buermeyer AB, Deschênes SM, Baker SM et al (1999) Mammalian DNA mismatch repair. Annu Rev Genet 33:533–564PubMedCrossRefGoogle Scholar
  8. 8.
    La Torre G, Chiaradia G, Gianfagna F et al (2009) Smoking status and gastric cancer risk: an updated meta-analysis of case-control studies published in the past ten years. Tumori 95:13–22PubMedGoogle Scholar
  9. 9.
    Corso G, Marrelli D, Pedrazzani C et al (2009) Gastric cardia carcinoma is associated with the promoter −77T > C gene polymorphism of X-ray cross-complementing group 1 (XRCC1). J Gastrointest Surg 13:2233–2238PubMedCrossRefGoogle Scholar
  10. 10.
    Guilford P, Hopkins JB, Grady WM et al (1999) E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Hum Mutat 14:249–255PubMedCrossRefGoogle Scholar
  11. 11.
    Berx G, Cleton-Jansen AM, Nollet F et al (1995) E-cadherin is a tumor/invasion suppressor gene mutated in human lobular breast cancers. EMBO J 14:6107–6115PubMedGoogle Scholar
  12. 12.
    Takeichi M (1991) Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251:451–1455CrossRefGoogle Scholar
  13. 13.
    Brooks-Wilson AR, Kaurah P, Suriano G et al (2004) Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J Med Genet 41:508–517PubMedCrossRefGoogle Scholar
  14. 14.
    Fitzgeral RC, Hardwick R, Huntsman D et al (2010) Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 47:436–444CrossRefGoogle Scholar
  15. 15.
    Guilford P, Humar B, Blair V (2010) Hereditary diffuse gastric cancer: translation of CDH1 germline mutations into clinical practice. Gastric Cancer 13:1–10PubMedCrossRefGoogle Scholar
  16. 16.
    Suriano G, Oliveira MJ, Huntsman DG et al (2003) E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells. Hum Mol Genet 15:3007–3016CrossRefGoogle Scholar
  17. 17.
    Charlton A, Blair V, Shaw D et al (2005) Hereditary diffuse gastric cancer: predominance of multiple foci of signet ring cell carcinoma in distal stomach and transitional zone. Gut 53:814–820CrossRefGoogle Scholar
  18. 18.
    Pedrazzani C, Corso G, Marrelli D et al (2007) E cadherin and diffuse gastric cancer. Surgery 142:645–657PubMedCrossRefGoogle Scholar
  19. 19.
    Rhyu MS (1996) Molecular mechanisms underlying hereditary nonpolyposis colorectal carcinoma. J Natl Cancer Inst 88:240–251PubMedCrossRefGoogle Scholar
  20. 20.
    Vasen HF (2000) Clinical diagnosis and management of hereditary colorectal cancer syndromes. J Clin Oncol 18:81S–92SPubMedGoogle Scholar
  21. 21.
    Boland CR, Goel A (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138:2073–2087PubMedCrossRefGoogle Scholar
  22. 22.
    Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348:919–932PubMedCrossRefGoogle Scholar
  23. 23.
    Watson P, Lynch HT (1993) Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 71:677–685PubMedCrossRefGoogle Scholar
  24. 24.
    Aarnio M, Sankila R, Pukkala E et al (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81:214–218PubMedCrossRefGoogle Scholar
  25. 25.
    Gylling A, Abdel-Rahman WM, Juhola M et al (2007) Is gastric cancer part of the tumour spectrum of hereditary non-polyposis colorectal cancer? A molecular genetic study. Gut 56:926–933PubMedCrossRefGoogle Scholar
  26. 26.
    Rodriguez-Bigas MA, Boland CR, Hamilton SR et al (1997) A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 89:1758–1762PubMedCrossRefGoogle Scholar
  27. 27.
    Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268PubMedCrossRefGoogle Scholar
  28. 28.
    Vasen HF (2005) Clinical description of the Lynch syndrome [hereditary nonpolyposis colorectal cancer (HNPCC)]. Fam Cancer 4:219–225PubMedCrossRefGoogle Scholar
  29. 29.
    Birch JM, Alston RD, McNally RJ et al (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20:4621–4628PubMedCrossRefGoogle Scholar
  30. 30.
    Olivier M, Goldgar DE, Sodha N et al (2003) Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res 63:6643–6650PubMedGoogle Scholar
  31. 31.
    Li FP, Fraumeni JF, Jr, Mulvihill JJ, Blattner WA et al. (1988) A cancer family syndrome in twenty-four kindreds. Cancer Research 485358–485362Google Scholar
  32. 32.
    Birch JM, Hartley AL, Tricker KJ et al (1994) Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res 54:1298–1304PubMedGoogle Scholar
  33. 33.
    Varlery JM (2003) Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat 21:313–320CrossRefGoogle Scholar
  34. 34.
    Chompret A (2002) The Li-Fraumeni syndrome. Biochimie 84:75–82PubMedCrossRefGoogle Scholar
  35. 35.
    Oliveira C, Ferreira P, Nabais S et al (2004) E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients. Eur J Cancer 40:1897–1903PubMedCrossRefGoogle Scholar
  36. 36.
    Sugano K, Taniguchi T, Saeki M et al (1999) Germline p53 mutation in a case of Li-Fraumeni syndrome presenting gastric cancer. Jpn J Clin Oncol 29:513–516PubMedCrossRefGoogle Scholar
  37. 37.
    Kim IJ, Kang HC, Shin Y et al (2004) A TP53-truncating germline mutation (E287×) in a family with characteristics of both hereditary diffuse gastric cancer and Li-Fraumeni syndrome. J Hum Genet 49:591–595PubMedCrossRefGoogle Scholar
  38. 38.
    Keller G, Vogelsang H, Becker I et al (2004) Germline mutations of the E-cadherin (CDH1) and TP53 genes, rather than of RUNX3 and HPP1, contribute to genetic predisposition in German gastric cancer patients. J Med Genet 41:89CrossRefGoogle Scholar
  39. 39.
    Kusano M, Kakiuchi H, Mihara M et al (2001) Absence of microsatellite instability and germline mutations of E-cadherin, APC and p53 genes in Japanese familial gastric cancer. Tumor Biology 22:262–268PubMedCrossRefGoogle Scholar
  40. 40.
    Corso G, Pedrazzani C, Marrelli D et al (2010) Familial gastric cancer and Li-Fraumeni syndrome. Eur J Cancer Care 19:377–381CrossRefGoogle Scholar
  41. 41.
    Peutz JLA (1921) Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane. Nederl Maandschr Geneesk 10:134–46Google Scholar
  42. 42.
    Jeghers H, McKusick VA, Katz HA et al (1949) Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significante. N Engl J Med 241:1031–1036PubMedCrossRefGoogle Scholar
  43. 43.
    Van Lier MGF, Wagner A, Mathus-Vligen EMH et al (2010) High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance reccomendations. Am J Gastroenterol 105:1258–1264PubMedCrossRefGoogle Scholar
  44. 44.
    Lim W, Hearle N, Shah B et al (2003) Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. Br J Cancer 89:308–313PubMedCrossRefGoogle Scholar
  45. 45.
    Suriano G, Seixas S, Rocha J et al (2006) A model to infer the pathogenic significance of CDH1 germline missense variants. J Mol Med 84:1023–1031PubMedCrossRefGoogle Scholar
  46. 46.
    Lindor NM, Petersen GM, Hadley DW et al. (2006) Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 2006 296:1507–1517Google Scholar
  47. 47.
    Hendriks YM, de Jong AE, Morreau H et al (2006) Diagnostic approach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma): a guide for clinicians. CA Cancer J Clin 56:213–225PubMedCrossRefGoogle Scholar
  48. 48.
    Roviello F, Corso G, Pedrazzani C et al (2007) High incidence of familial history in Tuscany, a region in Italy. Oncology 72:243–247PubMedCrossRefGoogle Scholar
  49. 49.
    Roviello F, Corso G, Pedrazzani C et al (2007) Hereditary diffuse gastric cancer and E-cadherin: description of the first germline mutation in an Italian family. Eur J Surg Oncol 33:448–451PubMedCrossRefGoogle Scholar
  50. 50.
    Corso G, Pedrazzani C, Pinheiro H et al. (2010) E-cadherin genetic screening and clinico-pathologic characteristics of early onset gastric cancer. Eur J Cancer in pressGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Giovanni Corso
    • 1
    • 2
    • 3
  • Daniele Marrelli
    • 1
    • 2
  • Franco Roviello
    • 1
    • 2
  1. 1.Department of Human Pathology and Oncology, Section of General Surgery and Surgical Oncology, Translational Research LaboratoryUniversity of SienaSienaItaly
  2. 2.Istituto Toscano Tumori (ITT)FlorenceItaly
  3. 3.Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP)PortoPortugal

Personalised recommendations