Geographical distribution of e‐cadherin germline mutations in the context of diffuse gastric cancer: A systematic review

Giovanni Corso, Federica Corso, Federica Bellerba, Patrícia Carneiro, Susana Seixas, Antonio Cioffi, Carlo La Vecchia, Francesca Magnoni, Bernardo Bonanni, Paolo Veronesi, Sara Gandini, Joana Figueiredo

Research output: Contribution to journalReview articlepeer-review


Hereditary diffuse gastric cancer (HDGC) is a complex and multifactorial inherited cancer predisposition syndrome caused by CDH1 germline mutations. Nevertheless, current CDH1 genetic screening recommendations disregard an unbalanced worldwide distribution of CDH1 variants, impacting testing efficacy and patient management. In this systematic review, we collected and analyzed all studies describing CDH1 variants in gastric cancer patients originating from both highand low‐prevalence countries. Selected studies were categorized as family study, series study, and unknown study, according to the implementation of HDGC clinical criteria for genetic testing. Our results indicate that CDH1 mutations are more frequently identified in gastric cancer low‐incidence countries, and in the family study group that encompasses cases fulfilling criteria. Considering the type of CDH1 alterations, we verified that the relative frequency of mutation types varies within study groups and geographical areas. In the series study, the missense variant frequency is higher in high‐incidence areas of gastric cancer, when compared with non‐missense mutations. However, application of variant scoring for putative relevance led to a strong reduction of CDH1 variants conferring increased risk of gastric cancer. Herein, we demonstrate that criteria for CDH1 genetic screening are critical for identification of individuals carrying mutations with clinical significance. Further, we propose that future guidelines for testing should consider GC incidence across geographical regions for improved surveillance programs and early diagnosis of disease.

Original languageEnglish
Article number1269
Pages (from-to)1-17
Number of pages17
Issue number6
Publication statusPublished - Mar 2 2021


  • Cancer geographical distribution
  • CDH1 mutation
  • E‐cadherin
  • Gastric cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Geographical distribution of e‐cadherin germline mutations in the context of diffuse gastric cancer: A systematic review'. Together they form a unique fingerprint.

Cite this