Hereditary diffuse gastric cancer

Czech version

Authors: P. Mlkvý ¹; M. Fritzmann ²; P. Minárik ¹; K. Macháleková ¹; I. Čavarga ¹; A. Mateášik ¹
Authors‘ workplace: Onkologický ústav Sv. Alžbety, Bratislava ¹; Interné oddelenie NsP, Partizánske ²
Published in: Gastroent Hepatol 2013; 67(5): 361-365
Category: Gastrointestinal Oncology: Review Article

Overview

Hereditary diffuse gastric cancer (HDGC) is an inherited form of the diffuse type of gastric cancer and a highly invasive type of tumour. Approximately 10% of patients with gastric cancer show familiar clustering and 3% autosomal dominance with a high HDGC penetration. It is an autosomal dominant inherited cancer syndrome in which affected individuals develop a diffuse type of gastric cancer at a young age. Inactivating mutations in the E-cadherin gene CDH1 have been identified in 30–50% of patients. CDH1 mutations carriers have an approximately 70% lifetime risk for developing diffuse gastric cancer (DGC) and affected women carry an additional 20–40% risk for developing lobular breast cancer. Common white light endoscopic surveillance is ineffective in identifying early HDGC. Gene-directed prophylactic total gastrectomy is currently being offered for CDH1 mutations carriers. Total gastrectomy is offered to patients who are five years younger than the youngest family member who developed gastric cancer, usually to patients older than 20. When refusing surgery, intensive endoscopic surveillance twice a year with multiple “protocol-based” and targeted biopsies combined with chromoendoscopy or NBI respectively are offered as an alternative option. Preventive total gastrectomy currently remains the only curative option for patients with HDGC.

Key words:
hereditary diffuse gastric cancer – mutation – gastrectomy

Sources

1. Guilford P, Hopkins J, Harraway J et al. E-cadherin germline mutations in familial gastric cancer. Nature 1998; 392(6674): 402–405.

2. Pleško I, Obšitníková A. Incidencia zhubných nádorov v Slovenskej republike. Národný onkologický register SR 2009.

3. Grady WM, Willis J, Guilford PJ et al. Methylation of CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet 2000; 26(1): 16–17.

4. 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. Gastroenterology 2001; 121(6): 1348–1353.

5. Oliveira C, Senz J ,Kaurah P et al. Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet 2009; 18(9): 1545–1555.

6. Keller G, Vogelsang H, Becker I et al. Diffuse type gastric and lobular breast carcinoma in a familial gastric patient with an E-cadherin germline mutation. Am J Pathol 1999; 155(2): 337–342.

7. Lynch HT, Silva E, Wirtzfeld D et al. Hereditary diffuse gastric cancer: prophylactic surgical oncology implications. Surg Clin North Am 2008; 88(4): 759–778.

8. Blair V, Martin I, Shaw D et al. Hereditary diffuse gastric cancer: diagnosis and management. Clin Gastroenterol Hepatol 2006; 4(3): 262–275.

9. Richards FM, McKee SA, Rajpar MH et al. Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Hum Mol Genet 1999; 8(4): 607–610.

10. Ikonen T, Matikainen M, Mononen N et al. Association of E-cadherin germ-line alterations with prostate cancer. Clin Cancer Res 2001; 7(11): 3465–3471.

11. Suriano G, Seixas S, Rocha J et al. A model to infer the pathogenic significance of CDH1 germline missense variants. J Mol Med (Berl) 2006; 84(12): 1023–1031.

12. Oliveira C, Seruca R, Carniero F. Genetics, pathology, and clinics of familial gastric cancer. Int J Surg Pathol 2006; 14(1): 21–33.

13. Guilford P, Blair V, More H et al. A short guide to hereditary diffuse gastric cancer. Hered Cancer Clin Pract 2007; 5(4): 183–194.

14. Fitzgerald RC, Hardwick R, Huntsman D et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 2010; 47(7): 436–444.

15. Charlton 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(6): 814–820.

16. Brooks-Wilson AR, Kaurah P, Suriano G et al. Germline E-cadherin mutations in hereditary diffuse gastric cancer. J Med Genet 2004; 41(7): 508–517.

17. Barber ME, Save V, Carneiro F et al. Histopathological and molecular analysis of gastrectomy specimens from hereditary diffuse gastric cancer patients has implications for endoscopic surveillance of individuals at risk. J Pathol 2008; 216(3): 286–294.

18. Cisco RM, Ford JM, Norton JA. Hereditary diffuse gastric cancer: implications of genetic testing for screening and prophylactic surgery. Cancer 2008; 113 (7 Suppl): 1850–1856.

19. Shaw D, Blair V, Framp A et al. Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy? Gut 2005; 54(4): 461–468.

20. Chen Y, Kingham K, Ford JM et al. A prospective study of total gastrectomy for CDH1-positive hereditary diffuse gastric cancer. Am Surg Oncol 2011; 18(9): 2594–2598.

21. Yoo CB , Jones PA. Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 2006; 5(1): 37–50.