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

Giovanni Corso,Franco Roviello,Daniele Marrelli,Valeria Pascale,Carla Vindigni

doi:10.1186/1471-2407-12-8

Giovanni Corso, Franco Roviello + Show 3 more

Open Access

https://doi.org/10.1186/1471-2407-12-8

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Abstract

BackgroundThe 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.MethodsEnglish 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.ResultsA 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).ConclusionsE-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.

Highlights

The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established
CDH1 germline mutations are associated with the development of the autosomal cancer syndrome namely Hereditary Diffuse Gastric Cancer (HDGC) [1,2]; about 25-30% of families fulfilling the clinical criteria for HDGC established by the International Gastric Cancer
The majority of selected studies were original reports We analysed a total of 212 studies; in detail 156 were excluded because they comprised somatic mutations, germline mutations in breast or colon cancers, molecular analyses, prophylactic gastrectomy descriptions and outdated reviews

Summary

Introduction

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. In GC patients coming from high-risk areas environmental factors, as specific foods, are more probably associated with the gastric carcinogenesis [8,9] in which genetic factors, as CDH1 or TP53 germline mutations, are very rarely identified [10,11,12,13,14,15]. To assess the CDH1 germline mutation frequency in low- and high-risk areas for GC, we reviewed all E-cadherin constitutional alterations identified from 1998 to date, considering the worldwide geographic distribution. We focused on low- and high-risk areas of gastric carcinoma in particular

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