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.

Geographical distribution of e‐cadherin germline mutations in the context of diffuse gastric cancer : A systematic review / G. Corso, F. Corso, F. Bellerba, P. Carneiro, S. Seixas, A. Cioffi, C. La Vecchia, F. Magnoni, B. Bonanni, P. Veronesi, S. Gandini, J. Figueiredo. - In: CANCERS. - ISSN 2072-6694. - 13:6(2021 Mar 12), pp. 1269.1-1269.17. [10.3390/cancers13061269]

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

G. Corso
;
C. La Vecchia;P. Veronesi;
2021

Abstract

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.
Cancer geographical distribution; CDH1 mutation; E‐cadherin; Gastric cancer
Settore MED/18 - Chirurgia Generale
Article (author)
File in questo prodotto:
File Dimensione Formato  
Germline gastric cancers-C_Corso_MDPI 13-01269-1.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.71 MB
Formato Adobe PDF
1.71 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/828233
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 12
social impact