Abstract
Individuals with CDH1 germline mutations are at high risk of develo** diffuse gastric cancer and prophylactic total gastrectomy represents the only life-saving treatment. Literature has reported a total of 224 surgical procedure in high-risk individuals, associated with germline CDH1 pathogenic mutations. The majority were described in the USA, the Netherlands, and Canada. Gastric tumor was identified in almost 85.4% of cases after prophylactic surgery, and a high rate of “no cancer” at histopathology was identified in the USA. Considering the mutation type, most of alterations were nonmissense versus missense sub-types. In this chapter, we will describe the penetrance risks for gastric cancer in CDH1 carriers and their implication for prophylactic gastrectomy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Pedrazzani C, Corso G, Marrelli D et al (2007) E-cadherin and hereditary diffuse gastric cancer. Surgery 142(5):645–657. https://doi.org/10.1016/j.surg.2007.06.006
Kluijt I, Siemerink EJ, Ausems MG et al (2012) CDH1-related hereditary diffuse gastric cancer syndrome: clinical variations and implications for counseling. Int J Cancer 131(2):367–376. https://doi.org/10.1002/ijc.26398
Blair VR, McLeod M, Carneiro F et al (2020) Hereditary diffuse gastric cancer: updated clinical practice guidelines. Lancet Oncol 21(8):e386–e397. https://doi.org/10.1016/S1470-2045(20)30219-9
Caldas C, Carneiro F, Lynch HT et al (1999) Familial gastric cancer: overview and guidelines for management. J Med Genet 36(12):873–880. https://doi.org/10.1136/jmg.36.12.873
Corso G, Corso F, Ballerba F et al (2021) Geographical distribution of E-cadherin germline mutations in the context of diffuse gastric cancer: a systematic review. Cancers 13(6):1269. https://doi.org/10.3390/cancers13061269
van der Post RS, Vogelaar IP, Carneiro F et al (2015) Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet 52:361e374. https://doi.org/10.1136/jmedgenet-2015-103094
Hansford S, Kaurah P, Li-Chang H et al (2015) Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol 1(1):23–32. https://doi.org/10.1001/jamaoncol.2014.168
Roberts ME, Ranola JM, Marshall ML et al (2019) Comparison of CDH1 penetrance estimates in clinically ascertained families vs families ascertained for multiple gastric cancers. JAMA Oncol 5(9):1325–1331. https://doi.org/10.1001/jamaoncol.2019.1208
**cola RM, Li S, Rodriguez N, Reinecke P et al (2019) Clinical features and cancer risk in families with pathogenic CDH1 variants irrespective of clinical criteria. J Med Genet 56(12):838–843. https://doi.org/10.1136/jmedgenet-2019-105991
Corso G, Montagna G, Figueiredo J et al (2020) Hereditary gastric and breast cancer syndromes related to CDH1 germline mutation: a multidisciplinary clinical 232 review. Cancers 12(6):1598. https://doi.org/10.3390/cancers12061598
Corso G (2022) Pleiotropic cancer manifestations of germline CDH1 mutations: risks and management. J Surg Oncol. https://doi.org/10.1002/jso.26847
DiBrito SR, Blair AB, Prasath V et al (2020) Total gastrectomy for CDH-1 mutation carriers: an institutional experience. J Surg Res 247:438e444. https://doi.org/10.1016/j.jss.2019.09.062
Hamilton JG, Long JM, Brandt AC et al (2019) Patients’ medical and psychosocial experiences after detection of a CDH1 variant with multigene panel testing. JCO Precis Oncol 3:PO.18.00300. https://doi.org/10.1200/PO.18.00300
Katona BW, Farengo Clark D, Domchek SM (2020) CDH1 on multigene panel testing: look before you leap. J Natl Cancer Inst 112:330e334. https://doi.org/10.1093/jnci/djz229
Corso G, Intra M, Trentin C et al (2016) CDH1 germline mutations and hereditary lobular breast cancer. Familial Cancer 15:215e219. https://doi.org/10.1007/s10689-016-9869-5
Corso G, Figueiredo J, La Vecchia C et al (2018) Hereditary lobular breast cancer with an emphasis on E-cadherin genetic defect. J Med Genet 55:431e441. https://doi.org/10.1136/jmedgenet-2018-105337
Corso G, Magnoni F, Nicastro V et al (2022) Global distribution of prophylactic total gastrectomy in E-cadherin (CDH1) mutations. Semin Oncol 49:130
Corso G, Marrelli D, Pascale V et al (2012) Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature. BMC Cancer 6(12):8. https://doi.org/10.1186/1471-2407-12-8
Stewart DR, Frone MN, Chanock SJ (2020) Stomaching multigene panel testing: what to do about CDH1? J Natl Cancer Inst 112(1):325–326. https://doi.org/10.1093/jnci/djz230
Lee K, Krempely K, Roberts ME et al (2018) Specifications of the ACMG/AMP variant 254 curation guidelines for the analysis of germline CDH1 sequence variants. Hum Mutat 39(11):1553–1568. https://doi.org/10.1002/humu.23650
Corso G (2020) Letter regarding: is prophylactic Total gastrectomy always indicated in CDH1 germline mutant carriers? J Surg Res 255:647–648. https://doi.org/10.1016/j.jss.2020.02.022
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Ferrara, F., Massari, G., Tagliaferri, V., Corso, G. (2023). Prophylactic Total Gastrectomy: How Many?. In: Corso, G., Veronesi, P., Roviello, F. (eds) Hereditary Gastric and Breast Cancer Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-031-21317-5_16
Download citation
DOI: https://doi.org/10.1007/978-3-031-21317-5_16
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-21316-8
Online ISBN: 978-3-031-21317-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)