Open Access Highly Accessed Research article

Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature

Giovanni Corso1*, Daniele Marrelli1, Valeria Pascale1, Carla Vindigni2 and Franco Roviello1

Author Affiliations

1 Department of Human Pathology and Oncology, section of General Surgery and Surgical Oncology, Translational Research Laboratory, University of Siena, Viale Bracci, 53100 Siena, Italy

2 Unit of Pathology, Hospital Santa Maria alle Scotte, Azienda Ospedaliera Universitaria Senese, Siena, Italy

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BMC Cancer 2012, 12:8  doi:10.1186/1471-2407-12-8

Published: 6 January 2012



The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established. The goal of this study was to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from low- and high-risk areas.


English articles using MEDLINE access (from 1998 to 2011). Search terms included CDH1, E-cadherin, germline mutation, gastric cancer, hereditary, familial and diffuse histotype.

The study included all E-cadherin germline mutations identified in gastric cancer patients; somatic mutations and germline mutations reported in other tumors were excluded.

The method of this study was scheduled in accordance with the "PRISMA statement for reporting systematic reviews and meta-analyses". Countries were classified as low- or middle/high risk-areas for gastric carcinoma incidence. Statistical analysis was performed to correlate the CDH1 mutation frequency with gastric cancer incidence areas.


A total of 122 E-cadherin germline mutations have been identified; the majority (87.5%) occurred in gastric cancers coming from low-risk areas. In high-risk areas, we identified 16 mutations in which missense mutations were predominant. (68.8%). We verified a significant association between the mutation frequency and the gastric cancer risk area (p < 0.001: overall identified mutations in low- vs. middle/high-risk areas).


E-cadherin genetic screenings performed in low-risk areas for gastric cancer identified a higher frequency of CDH1 germline mutations. This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the CDH1 genetic screening, geographic variability, alongside the family history should be considered.

Gastric cancer; E-cadherin; Germline mutation; Risk area