Hereditary Diffuse Gastric Cancer: Diagnosis and Management
2006; Elsevier BV; Volume: 4; Issue: 3 Linguagem: Inglês
10.1016/j.cgh.2005.12.003
ISSN1542-7714
AutoresVanessa Blair, Iain G. Martin, David W. Shaw, Ingrid Winship, Dale Kerr, Julie Arnold, Pauline Harawira, Maybelle McLeod, Susan Parry, Amanda Charlton, Michael Findlay, Brian Cox, Bostjan Humar, Helen More, Parry Guilford,
Tópico(s)Helicobacter pylori-related gastroenterology studies
ResumoHereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome defined by germline mutation of the E-cadherin gene (CDH-1). The cumulative risk for advanced gastric cancer in HDGC is 67% in men and 83% in women by 80 years of age. Early HDGC is characterized by multiple microscopic foci of intramucosal signet-ring cell carcinoma. The time to progression of these foci appears to be variable and currently is not predictable—the carcinoma foci may remain confined to the mucosa for many years. The management options for mutation carriers include prophylactic gastrectomy or surveillance gastroscopy. The only extensive published surveillance experience used chromogastroscopy, which detected early HDGC foci not visible on white-light endoscopy. The use of new techniques such as confocal microscopy, spectroscopy, or autofluorescence may prove useful, but have not been studied in HDGC. In patients up to 20 years of age, the risk for gastric cancer is less than 1%; this risk is outweighed by the mortality and morbidity associated with total gastrectomy. It is therefore recommended that genetic testing should occur at 16 years of age and that annual surveillance chromogastroscopy also should begin at age 16 in identified CDH-1 mutation carriers. After 20 years of age, delaying prophylactic gastrectomy carries significant risk, particularly if the alternative is surveillance by white-light gastroscopy. Surveillance chromogastroscopy (Congo red/methylene blue technique) should be considered for individuals younger than 20 years and patients unwilling to undergo prophylactic gastrectomy. Sufficient evidence for an increased risk for lobular breast cancer in CDH-1 carriers exists to justify breast screening in female carriers older than 35 years of age, however, evidence is insufficient to recommend prophylactic mastectomy. Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome defined by germline mutation of the E-cadherin gene (CDH-1). The cumulative risk for advanced gastric cancer in HDGC is 67% in men and 83% in women by 80 years of age. Early HDGC is characterized by multiple microscopic foci of intramucosal signet-ring cell carcinoma. The time to progression of these foci appears to be variable and currently is not predictable—the carcinoma foci may remain confined to the mucosa for many years. The management options for mutation carriers include prophylactic gastrectomy or surveillance gastroscopy. The only extensive published surveillance experience used chromogastroscopy, which detected early HDGC foci not visible on white-light endoscopy. The use of new techniques such as confocal microscopy, spectroscopy, or autofluorescence may prove useful, but have not been studied in HDGC. In patients up to 20 years of age, the risk for gastric cancer is less than 1%; this risk is outweighed by the mortality and morbidity associated with total gastrectomy. It is therefore recommended that genetic testing should occur at 16 years of age and that annual surveillance chromogastroscopy also should begin at age 16 in identified CDH-1 mutation carriers. After 20 years of age, delaying prophylactic gastrectomy carries significant risk, particularly if the alternative is surveillance by white-light gastroscopy. Surveillance chromogastroscopy (Congo red/methylene blue technique) should be considered for individuals younger than 20 years and patients unwilling to undergo prophylactic gastrectomy. Sufficient evidence for an increased risk for lobular breast cancer in CDH-1 carriers exists to justify breast screening in female carriers older than 35 years of age, however, evidence is insufficient to recommend prophylactic mastectomy. In 1998, genetic linkage analysis and subsequent mutation detection in a large New Zealand Maori family (family A) with early onset, multigenerational, diffuse gastric carcinoma identified the gene for the cell-to-cell adhesion protein, E-cadherin (CDH-1), as a novel cancer susceptibility gene.1Guilford P. Hopkins J. Harraway J. et al.E-cadherin germline mutations in familial gastric cancer.Nature. 1998; 392: 402-405Crossref PubMed Scopus (1363) Google Scholar This finding led to the identification of germline CDH-1 mutations in other gastric cancer families,2Gayther S.A. Gorringe K.L. Ramus S.J. et al.Identification of germ-line E-cadherin mutations in gastric cancer families of European origin.Cancer Res. 1998; 58: 4086-4089PubMed Google Scholar, 3Richards F.M. McKee S.A. Rajpar M.H. et al.Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.Hum Mol Genet. 1999; 8: 607-610Crossref PubMed Scopus (282) Google Scholar, 4Guilford P. Hopkins J. Grady W. et al.E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.Hum Mutat. 1999; 14: 249-255Crossref PubMed Scopus (230) Google Scholar and the description of a new inherited cancer syndrome known as hereditary diffuse gastric cancer (HDGC).4Guilford P. Hopkins J. Grady W. et al.E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.Hum Mutat. 1999; 14: 249-255Crossref PubMed Scopus (230) Google Scholar Today, HDGC remains the only highly penetrant inherited susceptibility identified in kindred in whom gastric cancer is the predominant malignancy. Appropriate clinical management of asymptomatic individuals presenting with a family history of gastric cancer hinges on an accurate estimation of lifetime cancer risk. In the absence of an identified predisposing mutation, risk can be estimated only by using the number and age of affected first- and second-degree relatives. Individuals estimated to be at a high risk for gastric cancer can be offered surveillance gastroscopy, although the effectiveness of this approach currently is unproven. In the absence of proven inherited susceptibility, prophylactic total gastrectomy as an alternative to watchful waiting largely is precluded because of its perioperative mortality and considerable lifelong morbidity. Detection of a germline CDH-1 mutation enables a more accurate estimation of risk to inform decisions regarding surveillance gastroscopy and prophylactic gastrectomy. Guidelines on the management of familial gastric cancer were first published in 1999 by the International Gastric Cancer Linkage Consortium (IGCLC).5Caldas C. Carneiro F. Lynch H.T. et al.Familial gastric cancer overview and guidelines for management.J Med Genet. 1999; 36: 873-880PubMed Google Scholar Since then, additional articles have reported on CDH-1 mutation testing,6Keller G. Vogelsang H. Becker I. et al.Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation.Am J Pathol. 1999; 155: 337-342Abstract Full Text Full Text PDF PubMed Scopus (252) Google Scholar, 7Shinmura K. Kohno T. Takahashi M. et al.Familial gastric cancer clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations.Carcinogenesis. 1999; 20: 1127-1131Crossref PubMed Scopus (126) Google Scholar, 8Yoon K.A. Ku J.L. Yang H.K. et al.Germline mutations of E-cadherin gene in Korean familial gastric cancer patients.J Hum Genet. 1999; 44: 177-180Crossref PubMed Scopus (85) Google Scholar, 9Dussaulx-Garin L. Blayau M. Pagenault M. et al.A new mutation of E-cadherin gene in familial gastric linitis plastica cancer with extra-digestive dissemination.Eur J Gastroenterol Hepatol. 2001; 13: 711-715Crossref PubMed Scopus (45) Google Scholar, 10Ascano J.J. Frierson H. Moskaluk C.A. et al.Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.Mod Pathol. 2001; 14: 943-949Crossref Scopus (58) Google Scholar, 11Humar B. Toro T.T. Graziano F. et al.Novel Germline CDH-1 mutations in hereditary diffuse gastric cancer families.Hum Mutat. 2002; 19: 518-525Crossref PubMed Scopus (57) Google Scholar, 12Oliveira C. Bordin M.C. Grehan N. et al.Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.Hum Mutat. 2002; 19: 510-517Crossref PubMed Scopus (144) Google Scholar, 13Yabuta T. Shinmura K. Tani M. et al.E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer.Int J Cancer. 2002; 101: 434-441Crossref PubMed Scopus (79) Google Scholar, 14Suriano G. Oliveira C. Ferreira P. et al.Identification of CDH-1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands.Hum Mol Genet. 2003; 12: 575-582Crossref PubMed Scopus (153) Google Scholar, 15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar, 16Keller G. Vogelsang H. Becker I. et al.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. 2004; 41: e89Crossref PubMed Scopus (94) Google Scholar, 17Wang Y. Song J.-P. Ikeda M. et al.Ile-Leu substitution (I415L) in germline E-cadherin gene (CDH-1) in Japanese familial gastric cancer.Jpn J Clin Oncol. 2003; 33: 17-20Crossref PubMed Scopus (35) Google Scholar, 18Jiang Y. Wan Y. Wang Z. et al.[Germline E-cadherin gene mutation screening in familial gastric cancer kindreds].Zhonghua Wai Ke Za Zhi. 2004; 42: 914-917PubMed Google Scholar genetic counseling,19Lynch H.T. Grady W. Lynch J.F. et al.E-cadherin mutation-based genetic counseling and hereditary diffuse gastric carcinoma.Cancer Genet Cytogenet. 2000; 122: 1-6Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar the cumulative risk for gastric and breast carcinoma,20Pharoah P. Guilford P. Caldas C. Consortium TIGCLIncidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families.Gastroenterology. 2001; 121: 1348-1353Abstract Full Text Full Text PDF PubMed Scopus (488) Google Scholar prophylactic gastrectomy,21Lewis F.R. Mellinger J.D. Hayashi A. et al.Prophylactic total gastrectomy for familial cancer.Surgery. 2001; 130: 612-619Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 22Chun Y.S. Lindor N.M. Smyrk T.C. et al.Germline E-cadherin mutations is prophylactic gastrectomy indicated?.Cancer. 2001; 92: 181-187Crossref PubMed Scopus (132) Google Scholar, 23Fitzgerald R.C. Caldas C. Clinical implications of E-cadherin associated hereditary diffuse gastric cancer.Gut. 2004; 53: 775-778Crossref PubMed Scopus (83) Google Scholar early gastric pathology,24Huntsman D.G. Carneiro F. Lewis F.R. et al.Early gastric cancer in young asymptomatic carriers of germline E-cadherin mutations.N Engl J Med. 2001; 344: 1904-1909Crossref PubMed Scopus (357) Google Scholar, 25Charlton A. Blair V. Shaw D. et al.Hereditary diffuse gastric cancer predominance of multiple foci of signet ring cell carcinoma in distal stomach and transitional zone.Gut. 2004; 53: 814-820Crossref PubMed Scopus (140) Google Scholar, 26Carneiro F. Huntsman D.G. Smyrk T.C. et al.Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening.J Pathol. 2004; 203: 681-687Crossref PubMed Scopus (221) Google Scholar and surveillance chromogastroscopy.27Shaw D. Blair V. Framp A. et al.Chromoendoscopic surveillance in hereditary diffuse gastric cancer an alternative to prophylactic gastrectomy?.Gut. 2005; 54: 461-468Crossref PubMed Scopus (138) Google Scholar We recently reviewed the management of HDGC (The New Zealand HDGC Group annual meeting, March 29th, 2004, Auckland, New Zealand). Our aim was to reach consensus on the diagnosis and management of HDGC in New Zealand, including the recommended youngest age for CDH-1 genetic testing, surveillance gastroscopy, and prophylactic gastrectomy. The approach to diagnosis and management of HDGC in this article represents our agreed consensus statements. This article represents a comprehensive review of the literature on HDGC and germline E-cadherin mutations sourced through PubMed. The management approach presented is the consensus of the authors and other members of the New Zealand HDGC Group, based on the literature and collective clinical experience caring for HDGC patients. It is our practice to restrict the diagnosis of HDGC to families with identified CDH-1 mutations. Families that fulfill the IGCLC criteria5Caldas C. Carneiro F. Lynch H.T. et al.Familial gastric cancer overview and guidelines for management.J Med Genet. 1999; 36: 873-880PubMed Google Scholar but have no detected CDH-1 mutation are designated familial diffuse gastric cancer. HDGC is a relatively rare cancer syndrome. To date, germline CDH-1 mutations have been described in 45 families and 5 individual cases of gastric carcinoma (Table 1).1Guilford P. Hopkins J. Harraway J. et al.E-cadherin germline mutations in familial gastric cancer.Nature. 1998; 392: 402-405Crossref PubMed Scopus (1363) Google Scholar, 2Gayther S.A. Gorringe K.L. Ramus S.J. et al.Identification of germ-line E-cadherin mutations in gastric cancer families of European origin.Cancer Res. 1998; 58: 4086-4089PubMed Google Scholar, 3Richards F.M. McKee S.A. Rajpar M.H. et al.Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.Hum Mol Genet. 1999; 8: 607-610Crossref PubMed Scopus (282) Google Scholar, 4Guilford P. Hopkins J. Grady W. et al.E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.Hum Mutat. 1999; 14: 249-255Crossref PubMed Scopus (230) Google Scholar, 6Keller G. Vogelsang H. Becker I. et al.Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation.Am J Pathol. 1999; 155: 337-342Abstract Full Text Full Text PDF PubMed Scopus (252) Google Scholar, 7Shinmura K. Kohno T. Takahashi M. et al.Familial gastric cancer clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations.Carcinogenesis. 1999; 20: 1127-1131Crossref PubMed Scopus (126) Google Scholar, 8Yoon K.A. Ku J.L. Yang H.K. et al.Germline mutations of E-cadherin gene in Korean familial gastric cancer patients.J Hum Genet. 1999; 44: 177-180Crossref PubMed Scopus (85) Google Scholar, 9Dussaulx-Garin L. Blayau M. Pagenault M. et al.A new mutation of E-cadherin gene in familial gastric linitis plastica cancer with extra-digestive dissemination.Eur J Gastroenterol Hepatol. 2001; 13: 711-715Crossref PubMed Scopus (45) Google Scholar, 10Ascano J.J. Frierson H. Moskaluk C.A. et al.Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.Mod Pathol. 2001; 14: 943-949Crossref Scopus (58) Google Scholar, 11Humar B. Toro T.T. Graziano F. et al.Novel Germline CDH-1 mutations in hereditary diffuse gastric cancer families.Hum Mutat. 2002; 19: 518-525Crossref PubMed Scopus (57) Google Scholar, 12Oliveira C. Bordin M.C. Grehan N. et al.Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.Hum Mutat. 2002; 19: 510-517Crossref PubMed Scopus (144) Google Scholar, 13Yabuta T. Shinmura K. Tani M. et al.E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer.Int J Cancer. 2002; 101: 434-441Crossref PubMed Scopus (79) Google Scholar, 14Suriano G. Oliveira C. Ferreira P. et al.Identification of CDH-1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands.Hum Mol Genet. 2003; 12: 575-582Crossref PubMed Scopus (153) Google Scholar, 15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar, 16Keller G. Vogelsang H. Becker I. et al.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. 2004; 41: e89Crossref PubMed Scopus (94) Google Scholar, 17Wang Y. Song J.-P. Ikeda M. et al.Ile-Leu substitution (I415L) in germline E-cadherin gene (CDH-1) in Japanese familial gastric cancer.Jpn J Clin Oncol. 2003; 33: 17-20Crossref PubMed Scopus (35) Google Scholar, 18Jiang Y. Wan Y. Wang Z. et al.[Germline E-cadherin gene mutation screening in familial gastric cancer kindreds].Zhonghua Wai Ke Za Zhi. 2004; 42: 914-917PubMed Google Scholar Family A is the largest known HDGC kindred with 40 identified CDH-1 mutation carriers. Between 1965, when the history of family A was first published28Jones E. Familial gastric cancer.N Z Med J. 1964; 63: 287-296PubMed Google Scholar and 1998 when the causative mutation was identified, 25 family members died from gastric carcinoma at a median age of 33 years.Table 1Known HDGC Families: Germline CDH-1 Mutation Details, Number and Age of Affected Family Members and Other MalignanciesExon intronCDH-1 mutationEthnicity/country (if stated)Mutation typeGastric cancer cases (#DGC)Mean age of onset (range)Breast cancer cases (#lobular)Cancer other sitesβReference 145insTEuropeanInsertion4 (2)44 (30–67)1 (1)3 Co12Oliveira C. Bordin M.C. Grehan N. et al.Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.Hum Mutat. 2002; 19: 510-517Crossref PubMed Scopus (144) Google Scholarint149-2A→GEuropean/UKSplice site6 (4)49 (34–69)Lu, Co3Richards F.M. McKee S.A. Rajpar M.H. et al.Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.Hum Mol Genet. 1999; 8: 607-610Crossref PubMed Scopus (282) Google Scholar 253delCEuropeanDeletion2 (2)38 (28–48)Lu, Cx11Humar B. Toro T.T. Graziano F. et al.Novel Germline CDH-1 mutations in hereditary diffuse gastric cancer families.Hum Mutat. 2002; 19: 518-525Crossref PubMed Scopus (57) Google Scholar 259G→AEuropean/UKNonsense3 (3)38 (27–50)3Richards F.M. McKee S.A. Rajpar M.H. et al.Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.Hum Mol Genet. 1999; 8: 607-610Crossref PubMed Scopus (282) Google Scholar 270G→TEuropean/USANonsense4 (3)42 (38–46)3Leu, Ly4Guilford P. Hopkins J. Grady W. et al.E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.Hum Mutat. 1999; 14: 249-255Crossref PubMed Scopus (230) Google Scholar 3185G→TJapaneseMissense6 (1)59 (46–72)7Shinmura K. Kohno T. Takahashi M. et al.Familial gastric cancer clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations.Carcinogenesis. 1999; 20: 1127-1131Crossref PubMed Scopus (126) Google Scholar 3187C→TEuropean/USANonsense3 (2)62 (33–85)12 Co, Pr, 2 En2Gayther S.A. Gorringe K.L. Ramus S.J. et al.Identification of germ-line E-cadherin mutations in gastric cancer families of European origin.Cancer Res. 1998; 58: 4086-4089PubMed Google Scholar 3190C→TMaori/NZNonsense2 (2)aAge or details of some affected family members unknown.25 (22–28)aAge or details of some affected family members unknown.4Guilford P. Hopkins J. Grady W. et al.E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.Hum Mutat. 1999; 14: 249-255Crossref PubMed Scopus (230) Google Scholar 3283C→TEuropean/FranceNonsense4 (3)42 (34–47)29Dussaulx-Garin L. Blayau M. Pagenault M. et al.A new mutation of E-cadherin gene in familial gastric linitis plastica cancer with extra-digestive dissemination.Eur J Gastroenterol Hepatol. 2001; 13: 711-715Crossref PubMed Scopus (45) Google Scholar 3372delCEuropean/GermanyDeletion4 (2)37 (15–58)1 (1)6Keller G. Vogelsang H. Becker I. et al.Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation.Am J Pathol. 1999; 155: 337-342Abstract Full Text Full Text PDF PubMed Scopus (252) Google Scholar 3382delCEuropean/ItalyDeletion7 (1)46 (32–56)215Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 5586G→TEuropean/FranceNonsense4 (4)45 (31–55)4Guilford P. Hopkins J. Grady W. et al.E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.Hum Mutat. 1999; 14: 249-255Crossref PubMed Scopus (230) Google Scholarint5687 (+1)G > AEuropeanSplice site4 (1)43 (36–50)115Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 6731A→GKoreanMissense7 (1)42 (30–63)8Yoon K.A. Ku J.L. Yang H.K. et al.Germline mutations of E-cadherin gene in Korean familial gastric cancer patients.J Hum Genet. 1999; 44: 177-180Crossref PubMed Scopus (85) Google Scholar 6832G→APakistaniSplice site10 (6)37 (23–70)112Oliveira C. Bordin M.C. Grehan N. et al.Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.Hum Mutat. 2002; 19: 510-517Crossref PubMed Scopus (144) Google Scholar 7892G→AEuropeanMissense3 (2)34 (32–36)15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 71008G→TMaori/NZSplice site28 (9)33 (14–74)1 (1 bilateral)Co1Guilford P. Hopkins J. Harraway J. et al.E-cadherin germline mutations in familial gastric cancer.Nature. 1998; 392: 402-405Crossref PubMed Scopus (1363) Google Scholar 81018A→GEuropeanMissense239 (35–47)Ov12Oliveira C. Bordin M.C. Grehan N. et al.Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.Hum Mutat. 2002; 19: 510-517Crossref PubMed Scopus (144) Google Scholar 81064insTEuropeanInsertion3 (2)47 (34–58)15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 81134del8ins5European/SpainDeletion/insertion4 (3)30 (27–32)aAge or details of some affected family members unknown.15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholarint81137 + 1G→AAfrican-AmericanSplice site5 (4)42 (25–58)4Guilford P. Hopkins J. Grady W. et al.E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.Hum Mutat. 1999; 14: 249-255Crossref PubMed Scopus (230) Google Scholar 91212delCEuropeanDeletion5 (4)41 (17–61)415Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 91226T→CEuropeanMissense1 (1)51Co (SRC)15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 91243A→CJapaneseMissense5 (2)62 (60–63)17Wang Y. Song J.-P. Ikeda M. et al.Ile-Leu substitution (I415L) in germline E-cadherin gene (CDH-1) in Japanese familial gastric cancer.Jpn J Clin Oncol. 2003; 33: 17-20Crossref PubMed Scopus (35) Google Scholar 101460T→CKoreanMissense2 (1)46 (42–49)8Yoon K.A. Ku J.L. Yang H.K. et al.Germline mutations of E-cadherin gene in Korean familial gastric cancer patients.J Hum Genet. 1999; 44: 177-180Crossref PubMed Scopus (85) Google Scholar 101472insAEuropeanInsertion3 (2)35 (32–40)12Oliveira C. Bordin M.C. Grehan N. et al.Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.Hum Mutat. 2002; 19: 510-517Crossref PubMed Scopus (144) Google Scholar 101476delAGEuropeanDeletion2 (1)36 (32–40)15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 10nsChineseNSNS (1)NS1 (1)18Jiang Y. Wan Y. Wang Z. et al.[Germline E-cadherin gene mutation screening in familial gastric cancer kindreds].Zhonghua Wai Ke Za Zhi. 2004; 42: 914-917PubMed Google Scholarint101565 + 1G→TArabic/NZSplice site3 (2)52 (49–56)11Humar B. Toro T.T. Graziano F. et al.Novel Germline CDH-1 mutations in hereditary diffuse gastric cancer families.Hum Mutat. 2002; 19: 518-525Crossref PubMed Scopus (57) Google Scholar 111588insCEuropean/USAInsertion3 (3)50 (40–63)14Guilford P. Hopkins J. Grady W. et al.E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.Hum Mutat. 1999; 14: 249-255Crossref PubMed Scopus (230) Google Scholar 111619insGEuropean/GermanInsertion1 (1)291 (bilateral)Ab, Lu16Keller G. Vogelsang H. Becker I. et al.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. 2004; 41: e89Crossref PubMed Scopus (94) Google Scholar 111710delTAfrican-AmericanDeletion2 (2)24 (19–29)1Pr11Humar B. Toro T.T. Graziano F. et al.Novel Germline CDH-1 mutations in hereditary diffuse gastric cancer families.Hum Mutat. 2002; 19: 518-525Crossref PubMed Scopus (57) Google Scholar 111711 insGEuropean/USAInsertion9 (NS)45 (30–68)2Gayther S.A. Gorringe K.L. Ramus S.J. et al.Identification of germ-line E-cadherin mutations in gastric cancer families of European origin.Cancer Res. 1998; 58: 4086-4089PubMed Google Scholar 111711(+5)G/AEuropeanSplice site3 (3)45 (44–48)5 (1)15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 121779insCEuropeanInsertion3 (3)37 (33–42)15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 121792C→TMaori/NZNonsense3 (1)35 (30–41)Pan11Humar B. Toro T.T. Graziano F. et al.Novel Germline CDH-1 mutations in hereditary diffuse gastric cancer families.Hum Mutat. 2002; 19: 518-525Crossref PubMed Scopus (57) Google Scholar 121792C→TEuropean/CanadaNonsense6 (3)31 (23–43)2Gayther S.A. Gorringe K.L. Ramus S.J. et al.Identification of germ-line E-cadherin mutations in gastric cancer families of European origin.Cancer Res. 1998; 58: 4086-4089PubMed Google Scholar 132061delTGEuropeanDeletion2 (2)36 (24–47)15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 132095C→TMaori/NZNonsenseNS (1)NS1Guilford P. Hopkins J. Harraway J. et al.E-cadherin germline mutations in familial gastric cancer.Nature. 1998; 392: 402-405Crossref PubMed Scopus (1363) Google Scholar 142195G→AEuropeanMissense2 (2)53 (36–70)4 (2)15Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholarint142295 + 5G→AEuropeanSplice site4 (2)47 (44–52)11Humar B. Toro T.T. Graziano F. et al.Novel Germline CDH-1 mutations in hereditary diffuse gastric cancer families.Hum Mutat. 2002; 19: 518-525Crossref PubMed Scopus (57) Google Scholar 152310delCEuropeanDeletion8 (1)61 (42–79)aAge or details of some affected family members unknown.115Brooks-Wilson A.R. Kaurah P. Suriano G. et al.Germline E-cadherin mutations in hereditary diffuse gastric cancer assessment of 42 new families and review of genetic screening criteria.J Med Genet. 2004; 41: 508-517Crossref PubMed Scopus (309) Google Scholar 152381insCMaori/NZInsertion7 (2)30 (16–35)aAge or details of some affected family members unknown.11Guilford P. Hopkins J. Harraway J. et al.E-cadherin germline mutations in familial gastric cancer.Nature. 1998; 392: 402-405Crossref PubMed Scopus (1363) Google Scholar 152396C→GEuropean/GermanMissense3 (1 m)47 (41–52)aAge or details of some affected family members unknown.16Keller G. Vogelsang H. Becker I. et al.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. 2004; 41: e89Crossref PubMed Scopus (94) Google Scholar 162494G→AJapaneseMissense7 (1)NS13Yabuta T. Shinmura K. Tani M. et al.E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer.Int J Cancer. 2002; 101: 434-441Crossref PubMed
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