Familial Cancer

, Volume 8, Issue 3, pp 215–220

Evidence of tumor microsatellite instability in gastric cancer with familial aggregation

  • Corrado Pedrazzani
  • Giovanni Corso
  • Sérgia Velho
  • Marina Leite
  • Valeria Pascale
  • Francesca Bettarini
  • Daniele Marrelli
  • Raquel Seruca
  • Franco Roviello
Article

Abstract

About 90% of gastric cancer (GC) cases appear in a sporadic setting. Nonetheless, in high incidence areas high familial aggregation rates have been recently described. Microsatellite instability (MSI) is thought to be an important molecular phenotype both in sporadic GC and in tumors of the HNPCC spectrum. The aim of this study was to assess the frequency of MSI in GC with familial aggregation. Five quasimonomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21 and NR-27) were analyzed in 250 GC patients. Seventy-five patients (30%) had at least one-first-degree family member affected by GC and 63 patients (25.2%) showed MSI. The frequency of MSI was significantly higher in patients with a positive family history of GC (38.7%) compared to patients with other tumor types within the family (15.7%) or with a negative oncological familial history (21.9%, P = 0.004). Within cases with a positive familial oncological history, the MSI frequency in families with GC only was similar to the one observed in families with GC and colon cancer (P = 0.96). Nonetheless, in families with GC and lung cancer, the frequency of MSI was significantly lower (5.6%, P = 0.007). MSI occurs in GCs with familial aggregation. Similar MSI rates have been observed in GC patients with other family members affected by GC or colon cancer. The same does not occur in families with other members affected by lung cancer. Our data seem to suggest that familial aggregation for either GC alone or gastric and colon cancer share common etiological factors in contrast to families with gastric and lung cancers.

Keywords

Gastric cancer Family history Microsatellite instability 

References

  1. 1.
    Ekström AM, Serafini M, Nyrén O et al (2000) Dietary antioxidant intake and the risk of cardia cancer and noncardia cancer of the intestinal and diffuse types: a population-based case-control study in Sweden. Int J Cancer 87:133–140. doi:10.1002/1097-0215(20000701)87:1<133::AID-IJC20>3.0.CO;2-EPubMedCrossRefGoogle Scholar
  2. 2.
    Palli D, Galli M, Caporaso NE et al (1994) Family history and risk of stomach cancer in Italy. Cancer Epidemiol Biomarkers Prev 3:15–18PubMedGoogle Scholar
  3. 3.
    Carneiro F, Oliveira C, Suriano G et al (2008) Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer. J Clin Pathol 61:25–30. doi:10.1136/jcp.2006.043679 PubMedCrossRefGoogle Scholar
  4. 4.
    Roviello F, Corso G, Pedrazzani C et al (2007) High incidence of familial gastric cancer in Tuscany, a region in Italy. Oncology 72:243–247. doi:10.1159/000113015 PubMedCrossRefGoogle Scholar
  5. 5.
    Kawasaki K, Kanemitsu K, Yasuda T et al (2007) Family history of cancer in Japanese gastric cancer patients. Gastric Cancer 10:173–175. doi:10.1007/s10120-007-0427-6 PubMedCrossRefGoogle Scholar
  6. 6.
    Brenner H, Bode G, Boeing H (2000) Helicobacter pylori infection among offspring of patients with stomach cancer. Gastroenterology 118:31–35. doi:10.1016/S0016-5085(00)70411-2 PubMedCrossRefGoogle Scholar
  7. 7.
    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
  8. 8.
    Caldas C, Carneiro F, Lynch HT et al (1999) Familial gastric cancer: overview and guidelines for management. J Med Genet 36:873–880PubMedGoogle Scholar
  9. 9.
    Guilford P, Hopkins J, Harraway J et al (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392:402–405. doi:10.1038/32918 PubMedCrossRefGoogle Scholar
  10. 10.
    Pedrazzani C, Corso G, Marrelli D et al (2007) E-cadherin and hereditary diffuse gastric cancer. Surgery 142:645–657. doi:10.1016/j.surg.2007.06.006 PubMedCrossRefGoogle Scholar
  11. 11.
    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 40:1897–1903. doi:10.1016/j.ejca.2004.04.027 PubMedCrossRefGoogle Scholar
  12. 12.
    Lynch HT, Smyrk TC, Watson P et al (1993) Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104:1535–1549PubMedGoogle Scholar
  13. 13.
    Rhyu MG, Park WS, Meltzer SJ (1994) Microsatellite instability occurs frequently in human gastric carcinoma. Oncogene 9:29–32PubMedGoogle Scholar
  14. 14.
    Eshleman JR, Markowitz SD (1995) Microsatellite instability in inherited and sporadic neoplasms. Curr Opin Oncol 7:83–89PubMedCrossRefGoogle Scholar
  15. 15.
    Boland CR, Thibodeau SN, Hamilton SR et al (1998) A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257PubMedGoogle Scholar
  16. 16.
    Seruca R, Santos NR, David L et al (1995) Sporadic gastric carcinomas with microsatellite instability display a particular clinicopathologic profile. Int J Cancer 64:32–36. doi:10.1002/ijc.2910640108 PubMedCrossRefGoogle Scholar
  17. 17.
    dos Santos NR, Seruca R, Constância M et al (1996) Microsatellite instability at multiple loci in gastric carcinoma: clinicopathologic implications and prognosis. Gastroenterology 110:38–44. doi:10.1053/gast.1996.v110.pm8536886 PubMedCrossRefGoogle Scholar
  18. 18.
    Beghelli S, de Manzoni G, Barbi S et al (2006) Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers. Surgery 139:347–356. doi:10.1016/j.surg.2005.08.021 PubMedCrossRefGoogle Scholar
  19. 19.
    Corso G, Pedrazzani C, Marrelli D et al (2007) Microsatellite instability at multiple loci shows a strong correlation with better long-term survival in advanced gastric cancer cases. Arch Surg (in press)Google Scholar
  20. 20.
    Chong JM, Fukayama M, Hayashi Y et al (1994) Microsatellite instability in the progression of gastric carcinoma. Cancer Res 54:4595–4597PubMedGoogle Scholar
  21. 21.
    Strickler JG, Zheng J, Shu Q et al (1994) p53 mutations and microsatellite instability in sporadic gastric cancer: when guardians fail. Cancer Res 54:4750–4755PubMedGoogle Scholar
  22. 22.
    Keller G, Rotter M, Vogelsang H et al (1995) Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history. Am J Pathol 147:593–600PubMedGoogle Scholar
  23. 23.
    Ottini L, Palli D, Falchetti M et al (1997) Microsatellite instability in gastric cancer is associated with tumor location and family history in a high-risk population from Tuscany. Cancer Res 57:4523–4529PubMedGoogle Scholar
  24. 24.
    Suraweera N, Duval A, Reperant M et al (2002) Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 123:1804–1811. doi:10.1053/gast.2002.37070 PubMedCrossRefGoogle Scholar
  25. 25.
    Keller G, Grimm V, Vogelsang H et al (1996) Analysis for microsatellite instability and mutations of the DNA mismatch repair gene hMLH1 in familial gastric cancer. Int J Cancer 68:571–576. doi:10.1002/(SICI)1097-0215(19961127)68:5<571::AID-IJC3>3.0.CO;2-WPubMedCrossRefGoogle Scholar
  26. 26.
    Pinto M, Wu Y, Mensink RG et al (2008) Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype. Cancer Genet Cytogenet 180:110–114. doi:10.1016/j.cancergencyto.2007.09.022 PubMedCrossRefGoogle Scholar
  27. 27.
    Shinmura K, Yin W, Isogaki J et al (1997) Stage-dependent evaluation of microsatellite instability in gastric carcinoma with familial clustering. Cancer Epidemiol Biomarkers Prev 6:693–697PubMedGoogle Scholar
  28. 28.
    Buermeyer AB, Deschênes SM, Baker SM et al (1999) Mammalian DNA mismatch repair. Annu Rev Genet 33:533–564. doi:10.1146/annurev.genet.33.1.533 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Corrado Pedrazzani
    • 1
    • 2
  • Giovanni Corso
    • 1
    • 2
    • 3
  • Sérgia Velho
    • 3
  • Marina Leite
    • 3
  • Valeria Pascale
    • 1
    • 2
  • Francesca Bettarini
    • 1
    • 2
  • Daniele Marrelli
    • 1
    • 2
  • Raquel Seruca
    • 3
  • Franco Roviello
    • 1
    • 2
  1. 1.Department of Human Pathology and Oncology, Unit of Surgical OncologyUniversity of SienaSienaItaly
  2. 2.Istituto Toscano Tumori (ITT)PratoItaly
  3. 3.Research Group of Cancer GeneticsInstitute of Molecular Pathology and Immunology of the University of PortoPortoPortugal

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