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Molecular Pathology of Heredity Gastric Cancer

  • Lin Li
  • Xiangshan FanEmail author
Chapter

Abstract

Gastric cancer (GC) affects nearly one million individuals every year, and most of them are from China, Japan, and Korea. It is the fifth most common malignant tumor worldwide and the third leading cause of malignant tumor mortality with more than 723,000 deaths [1]. About 70–85% of individuals with GC die within 5 years of diagnosis, and the high mortality associated with GC is mainly a result of limited therapeutic methods and lacking of early diagnosis. Aggregation within families occurs in almost 10% of patients (5–30%), although most GCs are sporadic. Now we know that hereditary germline mutations lead to half of these familial cases [2, 3]. In regions where the incidence of GC is low, heritable pathogenic mutations, which leads to most familial cases, increase risk from birth. Truly hereditary cases, as some studies pointed out, account for 1–3% of the global burden of GC [4], and most of those are hereditary diffuse gastric cancer (HDGC). It is reported that, in about 40% of families affected by HDGC, the E-cadherin/CDH1 germline mutations can been found. It is very important to identify the inherited factors among patients with family histories of GC, in order to diagnose early and manage effectively. We usually use symptoms, such as different family individuals are diagnosed with cancer, the histological types are diffused adenocarcinoma, and the patients are young and with multiple cancer syndromes, to identify HDGC. Some cases of other hereditary tumor syndromes may also present GC, and thus the risk of GC should be taken into account in these patients. The hereditary cancer syndromes include the gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), familial intestinal gastric cancer (FIGC), Lynch syndrome (LS) caused by germline mutations in DNA mismatch repair genes and microsatellite instability, familial adenomatous polyposis (FAP) associated with germline APC mutations, MUTYH-associated polyposis (MAP) associated with MUTYH mutation, Peutz-Jeghers syndrome (PJS) caused by germline STK11 mutations , juvenile polyposis syndrome (JPS) associated with germline mutations in the BMPR1A and SMAD4 genes, hereditary breast-ovarian cancer syndromes (HBCS) related to germline mutations of BRCA1 and BRCA2, Li-Fraumeni syndrome (LFS) due to germline p53 mutations, and so on [5].

Keywords

Gastric Cancer Familial Adenomatous Polyposis Adenomatous Polyposis Coli Lynch Syndrome Gastric Polyp 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi: 10.3322/caac.21262.CrossRefPubMedGoogle Scholar
  2. 2.
    Richards FM, McKee SA, Rajpar MH, Cole TR, Evans DG, Jankowski JA, et al. Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Hum Mol Genet. 1999;8(4):607–10.CrossRefPubMedGoogle Scholar
  3. 3.
    van der Post RS, Vogelaar IP, Manders P, van der Kolk LE, Cats A, van Hest LP, et al. Accuracy of hereditary diffuse gastric cancer testing criteria and outcomes in patients with a germline mutation in CDH1. Gastroenterology. 2015;149(4):897–906. doi: 10.1053/j.gastro.2015.06.003.CrossRefPubMedGoogle Scholar
  4. 4.
    Setia N, Clark JW, Duda DG, Hong TS, Kwak EL, Mullen JT, et al. Familial gastric cancers. Oncologist. 2015;20(12):1365–77. doi: 10.1634/theoncologist.2015-0205.
  5. 5.
    Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol. 2015;16(2):e60–70. doi: 10.1016/S1470-2045(14)71016-2.CrossRefPubMedGoogle Scholar
  6. 6.
    Chen Y, Kingham K, Ford JM, Rosing J, Van Dam J, Jeffrey RB, et al. A prospective study of total gastrectomy for CDH1-positive hereditary diffuse gastric cancer. Ann Surg Oncol. 2011;18(9):2594–8. doi: 10.1245/s10434-011-1648-9.CrossRefPubMedGoogle Scholar
  7. 7.
    Winawer SJ. Gastric cancer: worldwide burden and prevention opportunities. Chin J Dig Dis. 2005;6(3):107–9. doi: 10.1111/j.1443-9573.2005.00211.x.CrossRefPubMedGoogle Scholar
  8. 8.
    Etemadi M, Pourian M, Shakib A, Sabokbar T, Peyghanbari V, Shirkoohi R. A registry program for familial gastric cancer patients referred to Cancer Institute of Iran. Asian Pac J Cancer Prev. 2014;15(5):2141–4.CrossRefPubMedGoogle Scholar
  9. 9.
    Donner I, Kiviluoto T, Ristimaki A, Aaltonen LA, Vahteristo P. Exome sequencing reveals three novel candidate predisposition genes for diffuse gastric cancer. Fam Cancer. 2015;14(2):241–6. doi: 10.1007/s10689-015-9778-z.CrossRefPubMedGoogle Scholar
  10. 10.
    Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010;47(7):436–44. doi: 10.1136/jmg.2009.074237.
  11. 11.
    Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392(6674):402–5. doi: 10.1038/32918.CrossRefPubMedGoogle Scholar
  12. 12.
    Gayther SA, Gorringe KL, Ramus SJ, Huntsman D, Roviello F, Grehan N, et al. Identification of germ-line E-cadherin mutations in gastric cancer families of European origin. Cancer Res. 1998;58(18):4086–9.PubMedGoogle Scholar
  13. 13.
    Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010;47(7):436–44.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Oliveira C, Senz J, Kaurah P, Pinheiro H, Sanges R, Haegert A, et al. Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet. 2009;18(9):1545–55.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Oliveira C, Senz J, Kaurah P, Pinheiro H, Sanges R, Haegert A, et al. Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet. 2009;18(9):1545–55. doi: 10.1093/hmg/ddp046.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. E-cadherin alterations in hereditary disorders with emphasis on hereditary diffuse gastric cancer. Prog Mol Biol Transl Sci. 2013;116:337–59. doi: 10.1016/B978-0-12-394311-8.00015-7.CrossRefPubMedGoogle Scholar
  17. 17.
    Carneiro F. Hereditary gastric cancer. Pathologe. 2012;33(Suppl 2):231–4. doi: 10.1007/s00292-012-1677-6.
  18. 18.
    Carneiro F, Oliveira C, Suriano G, Seruca R. Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer. J Clin Pathol. 2008;61(1):25–30.CrossRefPubMedGoogle Scholar
  19. 19.
    Majewski IJ, Kluijt I, Cats A, Scerri TS, de Jong D, Kluin RJ, et al. An alpha-E-catenin (CTNNA1) mutation in hereditary diffuse gastric cancer. J Pathol. 2013;229(4):621–9. doi: 10.1002/path.4152.CrossRefPubMedGoogle Scholar
  20. 20.
    Oliveira C, de Bruin J, Nabais S, Ligtenberg M, Moutinho C, Nagengast FM, et al. Intragenic deletion of CDH1 as the inactivating mechanism of the wild-type allele in an HDGC tumour. Oncogene. 2004;23(12):2236–40. doi: 10.1038/sj.onc.1207335.CrossRefPubMedGoogle Scholar
  21. 21.
    Grady WM, Willis J, Guilford PJ, Dunbier AK, Toro TT, Lynch H, et al. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000;26(1):16–7. doi: 10.1038/79120.CrossRefPubMedGoogle Scholar
  22. 22.
    Wm G, Ak GPD, Tt T, Lynch HWG, Ferguson K, Eng C, et al. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000;26(1):16–7.CrossRefGoogle Scholar
  23. 23.
    Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol. 2015;1(1):23–32. doi: 10.1001/jamaoncol.2014.168.CrossRefPubMedGoogle Scholar
  24. 24.
    Cisco RM, Ford JM, Norton JA. Hereditary diffuse gastric cancer: implications of genetic testing for screening and prophylactic surgery. Cancer. 2008;113(7 Suppl):1850–6. doi: 10.1002/cncr.23650.CrossRefPubMedGoogle Scholar
  25. 25.
    Worthley DL, Phillips KD, Wayte N, Schrader KA, Healey S, Kaurah P, et al. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut. 2012;61(5):774–9. doi: 10.1136/gutjnl-2011-300348.CrossRefPubMedGoogle Scholar
  26. 26.
    Yanarufujisawa R, Nakamura S, Moriyama T, Esaki M, Tsuchigame T, Gushima M, et al. Familial fundic gland polyposis with gastric cancer. Gut. 2012;61(7):1103–4.CrossRefGoogle Scholar
  27. 27.
    Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol. 2015;16(2):e60–70.CrossRefPubMedGoogle Scholar
  28. 28.
    Worthley DL, Phillips KD, Wayte N, Schrader KA, Healey S, Kaurah P, et al. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut. 2012;61(5):774–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Carneiro F, Oliveira C, Wen X, Seruca R. Familial gastric carcinoma. Diagn Histopathol. 2014;20(6):239–46.CrossRefGoogle Scholar
  30. 30.
    Li J, Woods SL, Healey S, Beesley J, Chen X, Lee JS, et al. Point mutations in Exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am J Hum Genet. 2016;98(5):830–42. doi: 10.1016/j.ajhg.2016.03.001.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, et al. Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(7):868–75. doi: 10.1200/JCO.2012.44.4612.CrossRefGoogle Scholar
  32. 32.
    Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM, et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology. 1993;104(5):1535–49.CrossRefPubMedGoogle Scholar
  33. 33.
    Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81(2):214–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Geary J, Sasieni P, Houlston R, Izatt L, Eeles R, Payne SJ, et al. Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC). Fam Cancer. 2008;7(2):163–72. doi: 10.1007/s10689-007-9164-6.
  35. 35.
    Soer EC, Leicher LW, Langers AM, van de Meeberg PC, van der Wouden EJ, Koornstra JJ, et al. Equivalent Helicobacter pylori infection rates in Lynch syndrome mutation carriers with and without a first-degree relative with gastric cancer. Int J Colorectal Dis. 2016;31(3):693–7. doi: 10.1007/s00384-016-2524-7.CrossRefPubMedGoogle Scholar
  36. 36.
    Boland CR, Koi M, Chang DK, Carethers JM. The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside. Fam Cancer. 2008;7(1):41–52. doi: 10.1007/s10689-007-9145-9.
  37. 37.
    Lipkin SM, Wang V, Jacoby R, Banerjee-Basu S, Baxevanis AD, Lynch HT, et al. MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet. 2000;24(1):27–35. doi: 10.1038/71643.CrossRefPubMedGoogle Scholar
  38. 38.
    Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21(6):1174–9.CrossRefGoogle Scholar
  39. 39.
    Syngal S, Fox EA, Eng C, Kolodner RD, Garber JE. Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J Med Genet. 2000;37(9):641–5.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Pinto M, Oliveira C, Machado JC, Cirnes L, Tavares J, Carneiro F, et al. MSI-L gastric carcinomas share the hMLH1 methylation status of MSI-H carcinomas but not their clinicopathological profile. Lab Invest. 2000;80(12):1915–23.CrossRefPubMedGoogle Scholar
  41. 41.
    Kashiwagi K, Watanabe M, Ezaki T, Kanai T, Ishii H, Mukai M, et al. Clinical usefulness of microsatellite instability for the prediction of gastric adenoma or adenocarcinoma in patients with chronic gastritis. Br J Cancer. 2000;82(11):1814–8. doi: 10.1054/bjoc.1999.1154.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Vasen HF. Clinical description of the Lynch syndrome [hereditary nonpolyposis colorectal cancer (HNPCC)]. Fam Cancer. 2005;4(3):219–25. doi: 10.1007/s10689-004-3906-5.CrossRefPubMedGoogle Scholar
  43. 43.
    Wahlberg SS, Schmeits J, Thomas G, Loda M, Garber J, Syngal S, et al. Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res. 2002;62(12):3485–92.PubMedGoogle Scholar
  44. 44.
    Musulen E, Moreno V, Reyes G, Sancho FJ, Peinado MA, Esteller M, et al. Standardized approach for microsatellite instability detection in gastric carcinomas. Hum Pathol. 2004;35(3):335–42.CrossRefPubMedGoogle Scholar
  45. 45.
    Nielsen M, Hes FJ, Nagengast FM, Weiss MM, Mathus-Vliegen EM, Morreau H, et al. Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis. Clin Genet. 2007;71(5):​427–33.CrossRefPubMedGoogle Scholar
  46. 46.
    Attard TM, Cuffari C, Tajouri T, Stoner JA, Eisenberg MT, Yardley JH, et al. Multicenter experience with upper gastrointestinal polyps in pediatric patients with familial adenomatous polyposis. Am J Gastroenterol. 2004;99(4):681–6. doi: 10.1111/j.1572-0241.2004.04115.x.CrossRefPubMedGoogle Scholar
  47. 47.
    Bianchi LK, Burke CA, Bennett AE, Lopez R, Hasson H, Church JM. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2008;6(2):180–5. doi: 10.1016/j.cgh.2007.11.018.CrossRefPubMedGoogle Scholar
  48. 48.
    Lynch HT, Smyrk T, McGinn T, Lanspa S, Cavalieri J, Lynch J, et al. Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP. Cancer. 1995;76(12):2427–33.CrossRefPubMedGoogle Scholar
  49. 49.
    Yamaguchi T, Ishida H, Ueno H, Kobayashi H, Hinoi T, Inoue Y, et al. Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients. Jpn J Clin Oncol. 2016;46(4):310–5.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Park JG, Park KJ, Ahn YO, Song IS, Choi KW, Hong YM, et al. Risk of gastric cancer among Korean familial adenomatous polyposis patients. Dis Colon Rectum. 1992;35(10):996–8.CrossRefPubMedGoogle Scholar
  51. 51.
    Da LMA, Church JM, Burke CA. The evolution of prophylactic colorectal surgery for familial adenomatous polyposis. Dis Colon Rectum. 2009;52(8):1481–6.CrossRefGoogle Scholar
  52. 52.
    Vasen HF, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008;57(5):704–13. doi: 10.1136/gut.2007.136127.
  53. 53.
    Wu TT, Kornacki S, Rashid A, Yardley JH, Hamilton SR. Dysplasia and dysregulation of proliferation in foveolar and surface epithelia of fundic gland polyps from patients with familial adenomatous polyposis. Am J Surg Pathol. 1998;22(3):293–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Bertoni G, Sassatelli R, Nigrisoli E, Pennazio M, Tansini P, Arrigoni A, et al. Dysplastic changes in gastric fundic gland polyps of patients with familial adenomatous polyposis. Ital J Gastroenterol Hepatol. 1999;31(3):192–7.PubMedGoogle Scholar
  55. 55.
    Nielsen M, Morreau H, Vasen HF, Hes FJ. MUTYH-associated polyposis (MAP). Crit Rev Oncol Hematol. 2011;79(1):1–16.CrossRefPubMedGoogle Scholar
  56. 56.
    Schneider C, Simon T, Hero B, Uphoff US, Drebber U, Alakus H, et al. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography-positive gastric adenocarcinoma in a 12-year-old girl with Peutz-Jeghers syndrome. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(14):e140–3.CrossRefGoogle Scholar
  57. 57.
    Lier MGFV, Wagner A, Mathus-Vliegen EMH, Kuipers EJ, Steyerberg EW, Leerdam MEV. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010;105(6):1258–64.CrossRefPubMedGoogle Scholar
  58. 58.
    Hemminki A, Avizienyte E, Roth S, Loukola A, Aaltonen LA, Järvinen H, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 1998;391(6663):184–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Amos CI, Keithericheteri MB, Sabripour M, Wei C, Mcgarrity TJ, Seldin MF, et al. Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet. 2004;41(5):327–33.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Jass JR, Williams CB, Bussey HJ, Morson BC. Juvenile polyposis—a precancerous condition. Histopathology. 1988;13(6):619–30.CrossRefPubMedGoogle Scholar
  61. 61.
    Howe JR, Sayed MG, Ahmed AF, Ringold J, Larsen-Haidle J, Merg A, et al. The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. J Med Genet. 2004;41(7):484–91.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Sayed MG, Ahmed AF, Ringold JR, Anderson ME, Bair JL, Mitros FA, et al. Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. Ann Surg Oncol. 2002;9(9):901–6.CrossRefPubMedGoogle Scholar
  63. 63.
    Latchford AR, Neale K, Phillips RK, Clark SK. Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome. Dis Colon Rectum. 2012;55(55):1038–43.CrossRefPubMedGoogle Scholar
  64. 64.
    Schreibman IR, Baker M, Amos C, Mcgarrity TJ. The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol. 2005;100(2):476–90.CrossRefPubMedGoogle Scholar
  65. 65.
    van Hattem WA, Brosens LA, de Leng WW, Morsink FH, Lens S, Carvalho R, et al. Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis. Gut. 2008;57(5):623–7. doi: 10.1136/gut.2007.142927.CrossRefPubMedGoogle Scholar
  66. 66.
    Masciari S, Dewanwala A, Stoffel EM, Lauwers GY, Zheng H, Achatz MI, et al. Gastric cancer in individuals with Li-Fraumeni syndrome. Genet Med. 2011;13(7):651–7. doi: 10.1097/GIM.0b013e31821628b6.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Chang VY, Federman N, Martinez-Agosto J, Tatishchev SF, Nelson SF. Whole exome sequencing of pediatric gastric adenocarcinoma reveals an atypical presentation of Li-Fraumeni syndrome. Pediatr Blood Cancer. 2013;60(4):570–4. doi: 10.1002/pbc.24316.CrossRefPubMedGoogle Scholar
  68. 68.
    da Silva EM, Achatz MI, Martel-Planche G, Montagnini AL, Olivier M, Prolla PA, et al. TP53 mutation p.R337H in gastric cancer tissues of a 12-year-old male child: evidence for chimerism involving a common mutant founder haplotype: case report. BMC Cancer. 2011;11:449. doi: 10.1186/1471-2407-11-449.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Chen XR, Zhang WZ, Lin XQ, Wang JW. Genetic instability of BRCA1 gene at locus D17S855 is related to clinicopathological behaviors of gastric cancer from Chinese population. World J Gastroe​nterol. 2006;12(26):4246–9.Google Scholar
  70. 70.
    Figer A, Irmin L, Geva R, Flex D, Sulkes J, Sulkes A, et al. The rate of the 6174delT founder Jewish mutation in BRCA2 in patients with non-colonic gastrointestinal tract tumours in Israel. Br J Cancer. 2001;84(4):478–81. doi: 10.1054/bjoc.2000.1605.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Lawniczak M, Jakubowska A, Bialek A, Lubinski J, Jaworska-Bieniek K, Kaczmarek K, et al. BRCA1 founder mutations do not contribute to increased risk of gastric cancer in the Polish population. Hered Cancer Clin Pract. 2016;14:3. doi: 10.1186/s13053-015-0043-0.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Trufant JW, Greene L, Cook DL, Mckinnon W, Greenblatt M, Bosenberg MW. Colonic ganglioneuromatous polyposis and metastatic adenocarcinoma in the setting of Cowden syndrome: a case report and literature review. Hum Pathol. 2012;43(4):601–4.CrossRefPubMedGoogle Scholar
  73. 73.
    Al-Thihli K, Palma L, Marcus V, Cesari M, Kushner YB, Barkun A, Foulkes WD. A case of Cowden’s syndrome presenting with gastric carcinomas and gastrointestinal polyposis. Nat Clin Pract Gastroenterol Hepatol. 2009;6(3):184–9.CrossRefPubMedGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Pathology of Drum Tower HospitalMedical School of Nanjing UniversityNanjingChina

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