• 1.中國醫(yī)學(xué)科學(xué)院 北京協(xié)和醫(yī)學(xué)院 北京協(xié)和醫(yī)院消化內(nèi)科（北京 100730）;;
  • 2.中國醫(yī)學(xué)科學(xué)院 北京協(xié)和醫(yī)學(xué)院 北京協(xié)和醫(yī)院基本外科（北京 100730）;

目的  綜述遺傳性彌漫型胃癌(hereditary diffuse gastric cancer，HDGC)與CDH1基因關(guān)系的研究進(jìn)展。方法  對近年國內(nèi)、外的相關(guān)文獻(xiàn)進(jìn)行整理分析。 結(jié)果  CDH1基因異常與HDGC有重要關(guān)系： CDH1基因外顯子突變是目前已知的、導(dǎo)致HDGC發(fā)病的最重要因素，篩查其突變情況可以用于指導(dǎo)HDGC的臨床診治； CDH1基因的其他改變，如內(nèi)含子突變、基因甲基化及單核苷酸多態(tài)性也可能影響其表達(dá)，但這些改變與HDGC發(fā)病的確切關(guān)系尚需進(jìn)一步研究。結(jié)論  CDH1基因的改變與HDGC的發(fā)生密切相關(guān)，檢測CDH1基因的變化對研究HDGC的病因及指導(dǎo)臨床診治有重要意義。

引用本文： 周春宇,陳原稼,李小毅. 遺傳性彌漫型胃癌與CDH1基因. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(11): 944-947. doi: 復(fù)制

1. Oliveira C, Seruca R, Carneiro F. Hereditary gastric cancer [J]. Best Pract Res Clin Gastroenterol, 2009; 23(2): 147-157.
2. Guilford P, Hopkins J, Harraway J, et al. E-cadherin germline mutations in familial gastric cancer [J]. Nature, 1998; 392(6674): 402-405.
3. van Kouwen MC, Drenth JP, Oyen WJ, et al. [18F]Fluoro-2-deoxy-D-glucose positron emission tomography detects gastric carcinoma in an early stage in an asymptomatic E-cadherin mutation carrier [J]. Clin Cancer Res, 2004; 10(19): 6456-6459.
4. Shaw D, Blair V, Framp A, et al. Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy? [J]. Gut, 2005; 54(4): 461-468.
5. Caldas C, Carneiro F, Lynch HT, et al. Familial gastric ca-ncer: overview and guidelines for management [J]. J Med Genet, 1999; 36(12): 873-880.
6. Pharoah PD, Guilford P, Caldas C, et al. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families [J]. Gastroenterology, 2001; 121(6): 1348-1353.
7. Schrader KA, Masciari S, Boyd N. Hereditary diffuse gastric cancer: association with lobular breast cancer [J]. Fam Cancer, 2008; 7(1): 73-82.
8. Cisco RM, Norton JA. Hereditary diffuse gastric cancer: su-rgery, surveillance and unanswered questions [J]. Future Oncol, 2008; 4(4): 553-559.
9. Huntsman DG, Carneiro F, Lewis FR, et al. Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations [J]. N Engl J Med, 2001; 344(25): 1904-1909.
10. Rogers WM, Dobo E, Norton JA, et al. Risk-reducing total gastrectomy for germline mutations in E-cadherin (CDH1): pathologic findings with clinical implications [J]. Am J Surg Pathol, 2008; 32(6): 799-809.
11. Hayashi K, Burghardt RC, Bazer FW, et al. WNTs in the ovine uterus: potential regulation of periimplantation ovine conceptus development [J]. Endocrinology, 2007; 148(7): 3496-3506.
12. Salahshor S, Naidoo R, Serra S, et al. Frequent accumulation of nuclear E-cadherin and alterations in the Wnt signaling pathway in esophageal squamous cell carcinomas [J]. Mod Pathol, 2008; 21(3): 271-281.
13. De Wever O, Derycke L, Hendrix A, et al. Soluble cadherins as cancer biomarkers [J]. Clin Exp Metastasis, 2007; 24(8): 685-697.
14. Kaurah P, MacMillan A, Boyd N, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer [J]. JAMA, 2007; 297(21): 2360-2372.
15. Pedrazzani C, Corso G, Marrelli D, et al. E-cadherin and hereditary diffuse gastric cancer [J]. Surgery, 2007; 142(5): 645-657.
16. 朱正綱, 于穎彥, 張奕, 等. 胃癌/乳腺癌先證者家族性癌癥綜合征家系CDH1突變分析及病理學(xué)特征 [J]. 中華消化雜志, 2004; 24(6): 344-348.
17. 姜勇, 萬遠(yuǎn)廉, 王振軍, 等. 遺傳性彌漫型胃癌上皮型鈣黏素基因種系突變的檢測 [J]. 中華外科雜志, 2004; 42(15): 914-917.
18. González-Flecha B, Demple B. Homeostatic regulation of intracellular hydrogen peroxide concentration in aerobically growing Escherichia coli [J]. J Bacteriol, 1997; 179(2): 382-388.
19. González-Flecha B, Demple B. Role for the oxyS gene in regulation of intracellular hydrogen peroxide in Escherichia coli [J]. J Bacteriol, 1999; 181(12): 3833-3836.
20. Stemmler MP, Hecht A, Kemler R. E-cadherin intron 2 contains cis-regulatory elements essential for gene expression [J]. Development, 2005; 132(5): 965-976.
21. More H, Humar B, Weber W, et al. Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene [J]. Hum Mutat, 2007; 28(2): 203.
22. Richards FM, McKee SA, Rajpar MH, et al. Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer [J]. Hum Mol Genet, 1999; 8(4): 607-610.
23. Moran CJ, Joyce M, McAnena OJ. CDH1 associated gastric cancer: a report of a family and review of the literature [J]. Eur J Surg Oncol, 2005; 31(3): 259-264.
24. Grady WM, Willis J, Guilford PJ, et al. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer [J]. Nat Genet, 2000; 26(1): 16-17.
25. Barber M, Murrell A, Ito Y, et al. Mechanisms and sequelae of E-cadherin silencing in hereditary diffuse gastric cancer [J]. J Pathol, 2008; 216(3): 295-306.
26. Berx G, Becker KF, Hfler H, et al. Mutations of the human E-cadherin (CDH1) gene [J]. Hum Mutat, 1998; 12(4): 226-237.
27. Nasri S, More H, Graziano F, et al. A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: a case control study in an Italian population [J]. BMC Cancer, 2008; 8: 138.
28. Gao L, Nieters A, Brenner H. Meta-analysis: tumour invasion-related genetic polymorphisms and gastric cancer susceptibility [J]. Aliment Pharmacol Ther, 2008; 28(5): 565-573.
29. Humar B, Toro T, Graziano F, et al. Novel germline CDH1 mutations in hereditary diffuse gastric cancer families [J]. Hum Mutat, 2002; 19(5): 518-525.
30. 金凡, 周淑貞, 陶蓉芳， 等. 上海市區(qū)惡性腫瘤發(fā)病趨勢1972～1994年 [J]. 腫瘤， 1999; 19(5)： 255-258.
  1. 1. Oliveira C, Seruca R, Carneiro F. Hereditary gastric cancer [J]. Best Pract Res Clin Gastroenterol, 2009; 23(2): 147-157.
  2. 2. Guilford P, Hopkins J, Harraway J, et al. E-cadherin germline mutations in familial gastric cancer [J]. Nature, 1998; 392(6674): 402-405.
  3. 3. van Kouwen MC, Drenth JP, Oyen WJ, et al. [18F]Fluoro-2-deoxy-D-glucose positron emission tomography detects gastric carcinoma in an early stage in an asymptomatic E-cadherin mutation carrier [J]. Clin Cancer Res, 2004; 10(19): 6456-6459.
  4. 4. Shaw D, Blair V, Framp A, et al. Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy? [J]. Gut, 2005; 54(4): 461-468.
  5. 5. Caldas C, Carneiro F, Lynch HT, et al. Familial gastric ca-ncer: overview and guidelines for management [J]. J Med Genet, 1999; 36(12): 873-880.
  6. 6. Pharoah PD, Guilford P, Caldas C, et al. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families [J]. Gastroenterology, 2001; 121(6): 1348-1353.
  7. 7. Schrader KA, Masciari S, Boyd N. Hereditary diffuse gastric cancer: association with lobular breast cancer [J]. Fam Cancer, 2008; 7(1): 73-82.
  8. 8. Cisco RM, Norton JA. Hereditary diffuse gastric cancer: su-rgery, surveillance and unanswered questions [J]. Future Oncol, 2008; 4(4): 553-559.
  9. 9. Huntsman DG, Carneiro F, Lewis FR, et al. Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations [J]. N Engl J Med, 2001; 344(25): 1904-1909.
  10. 10. Rogers WM, Dobo E, Norton JA, et al. Risk-reducing total gastrectomy for germline mutations in E-cadherin (CDH1): pathologic findings with clinical implications [J]. Am J Surg Pathol, 2008; 32(6): 799-809.
  11. 11. Hayashi K, Burghardt RC, Bazer FW, et al. WNTs in the ovine uterus: potential regulation of periimplantation ovine conceptus development [J]. Endocrinology, 2007; 148(7): 3496-3506.
  12. 12. Salahshor S, Naidoo R, Serra S, et al. Frequent accumulation of nuclear E-cadherin and alterations in the Wnt signaling pathway in esophageal squamous cell carcinomas [J]. Mod Pathol, 2008; 21(3): 271-281.
  13. 13. De Wever O, Derycke L, Hendrix A, et al. Soluble cadherins as cancer biomarkers [J]. Clin Exp Metastasis, 2007; 24(8): 685-697.
  14. 14. Kaurah P, MacMillan A, Boyd N, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer [J]. JAMA, 2007; 297(21): 2360-2372.
  15. 15. Pedrazzani C, Corso G, Marrelli D, et al. E-cadherin and hereditary diffuse gastric cancer [J]. Surgery, 2007; 142(5): 645-657.
  16. 16. 朱正綱, 于穎彥, 張奕, 等. 胃癌/乳腺癌先證者家族性癌癥綜合征家系CDH1突變分析及病理學(xué)特征 [J]. 中華消化雜志, 2004; 24(6): 344-348.
  17. 17. 姜勇, 萬遠(yuǎn)廉, 王振軍, 等. 遺傳性彌漫型胃癌上皮型鈣黏素基因種系突變的檢測 [J]. 中華外科雜志, 2004; 42(15): 914-917.
  18. 18. González-Flecha B, Demple B. Homeostatic regulation of intracellular hydrogen peroxide concentration in aerobically growing Escherichia coli [J]. J Bacteriol, 1997; 179(2): 382-388.
  19. 19. González-Flecha B, Demple B. Role for the oxyS gene in regulation of intracellular hydrogen peroxide in Escherichia coli [J]. J Bacteriol, 1999; 181(12): 3833-3836.
  20. 20. Stemmler MP, Hecht A, Kemler R. E-cadherin intron 2 contains cis-regulatory elements essential for gene expression [J]. Development, 2005; 132(5): 965-976.
  21. 21. More H, Humar B, Weber W, et al. Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene [J]. Hum Mutat, 2007; 28(2): 203.
  22. 22. Richards FM, McKee SA, Rajpar MH, et al. Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer [J]. Hum Mol Genet, 1999; 8(4): 607-610.
  23. 23. Moran CJ, Joyce M, McAnena OJ. CDH1 associated gastric cancer: a report of a family and review of the literature [J]. Eur J Surg Oncol, 2005; 31(3): 259-264.
  24. 24. Grady WM, Willis J, Guilford PJ, et al. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer [J]. Nat Genet, 2000; 26(1): 16-17.
  25. 25. Barber M, Murrell A, Ito Y, et al. Mechanisms and sequelae of E-cadherin silencing in hereditary diffuse gastric cancer [J]. J Pathol, 2008; 216(3): 295-306.
  26. 26. Berx G, Becker KF, Hfler H, et al. Mutations of the human E-cadherin (CDH1) gene [J]. Hum Mutat, 1998; 12(4): 226-237.
  27. 27. Nasri S, More H, Graziano F, et al. A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: a case control study in an Italian population [J]. BMC Cancer, 2008; 8: 138.
  28. 28. Gao L, Nieters A, Brenner H. Meta-analysis: tumour invasion-related genetic polymorphisms and gastric cancer susceptibility [J]. Aliment Pharmacol Ther, 2008; 28(5): 565-573.
  29. 29. Humar B, Toro T, Graziano F, et al. Novel germline CDH1 mutations in hereditary diffuse gastric cancer families [J]. Hum Mutat, 2002; 19(5): 518-525.
  30. 30. 金凡, 周淑貞, 陶蓉芳， 等. 上海市區(qū)惡性腫瘤發(fā)病趨勢1972～1994年 [J]. 腫瘤， 1999; 19(5)： 255-258.