SNFGE SNFGE
 
Thématique :
- Cancers autres
Originalité :
Intermédiaire
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Dans certains cas
 
 
Nom du veilleur :
Docteur Roger FAROUX
Coup de coeur :
 
 
Gastroenterology
  2015/11  
 
  Oct;149(4):897-906.e19  
  doi: 10.1053/j.gastro.2015.06.003  
 
  Accuracy of Hereditary Diffuse Gastric Cancer Testing Criteria and Outcomes in Patients With a Germline Mutation in CDH1  
 
  van der Post RS, Vogelaar IP, Manders P, van der Kolk LE, Cats A, van Hest LP, Sijmons R, Aalfs CM, Ausems MG, Gómez García EB, Wagner A, Hes FJ, Arts N, Mensenkamp AR, van Krieken JH, Hoogerbrugge N, Ligtenberg MJ  
  http://www.ncbi.nlm.nih.gov/pubmed/26072394  
 
 

BACKGROUND & AIMS:

Germline mutations in the cadherin 1, type 1, E-cadherin gene (CDH1) cause a predisposition to gastric cancer. We evaluated the ability of the internationally accepted hereditary diffuse gastric cancer (HDGC) criteria to identify individuals with pathogenic mutations in CDH1, and assessed their outcomes. The criteria were as follows: families with 2 or more cases of gastric cancer, with at least 1 patient diagnosed with diffuse gastric cancer (DGC) before age 50; families with 3 or more cases of DGC; families with 1 DGC before the age of 40; and families with a history of DGC and lobular breast cancer, with 1 diagnosis before the age of 50.

METHODS:

We collected results of a CDH1 mutation analysis of 578 individuals from 499 families tested in The Netherlands between 1999 and 2014 (118 families met the HDGC criteria for testing and 236 did not; there were 145 families with incomplete data and/or availability of only first-degree relatives). Data were linked with family histories and findings from clinical and pathology analyses. The Kaplan-Meier method and Cox regression analysis were used to evaluate the overall survival of patients with and without CDH1 mutations.

RESULTS:

In a cohort study in The Netherlands, the HDGC criteria identified individuals with a germline CDH1 mutation with a positive predictive value of 14% and 89% sensitivity. There were 18 pathogenic CDH1 mutations in 499 families (4%); 16 of these mutations were detected in the 118 families who met the HDGC criteria for testing. One pathogenic CDH1 mutation was detected in the 236 families who did not meet HDGC criteria and 1 in the 145 families with incomplete data and/or availability of only first-degree relatives. No CDH1 mutations were found in the 67 families whose members developed intestinal-type gastric cancer, or in the 22 families whose families developed lobular breast cancer. Among patients who fulfilled the HDGC criteria and had pathogenic CDH1 mutations, 36% survived for 1 year and 4% survived for 5 years; among patients who fulfilled the HDGC criteria but did not carry pathogenic CDH1 mutations, 48% survived for 1 year and 13% survived for 5 years (P = .014 for comparative survival analysis between patients with and without a CDH1 mutation).

CONCLUSIONS:

All individuals with a CDH1 mutation had a personal or family history of diffuse gastric cancer. Patients with gastric cancer and germline CDH1 mutations had shorter survival times than patients who met the HDGC criteria but did not have CDH1 mutations.

 
Question posée
 
La mutation de CDH1permet-elle d’individualiser des sujets à plus mauvais pronostic au sein des familles répondant aux critères clinique des cancers gastriques héréditaires diffus (CGHD) ?
 
Question posée
 
oui.
 
Commentaires

La recherche d’une  mutation constitutionnelle de CDH1 qui code pour la protéine d’adhésion  E-Cadherine doit être proposée lors d’une consultation d’oncogénétique  en cas de positivité des critères cliniques de CGHD 

 
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