期刊
CANCERS
卷 13, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/cancers13061269
关键词
gastric cancer; E-cadherin; CDH1 mutation; cancer geographical distribution
类别
资金
- Italian Ministry of Health [GR-2016-02361655]
- Ricerca Corrente fund
- FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE 2020)
- Programa Operacional de Competitividade e Internacionalizacao (POCI)
- Programa Operacional Regional do Norte (Norte 2020)
- Portuguese Foundation for Science and Technology (FCT) [PTDC/MED-GEN/30356/2017, PTDC/BIM-ONC/0281/2014]
- American Association of Patients with Hereditary Gastric Cancer No Stomach for Cancer
- 5 x 1000 fund
- Fundação para a Ciência e a Tecnologia [PTDC/BIM-ONC/0281/2014, PTDC/MED-GEN/30356/2017] Funding Source: FCT
E-cadherin germline mutations, particularly CDH1 gene mutations, are associated with hereditary diffuse gastric cancer syndrome. The frequency of CDH1 mutations varies across different geographical areas, with a higher incidence in low-prevalence countries. The type and relative frequency of CDH1 mutations also differ between study groups and regions, with missense variants more common in high-incidence areas. Identifying individuals with clinically significant CDH1 mutations is crucial for effective genetic screening and patient management in gastric cancer.
Simple Summary E-cadherin (CDH1 gene) germline mutations are associated with the development of the autosomal cancer syndrome known as hereditary diffuse gastric cancer. About 30% of families fulfilling the clinical criteria established by the International Gastric Cancer Linkage Consortium have constitutional alterations of the CDH1 gene. Different patterns of CDH1 germline mutations have described as truncating, deletion, insertion, splice site, non sense, silence, and at last, missense alterations. The frequency of the different E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has reported extremely variable. In this study we aimed to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from different geographical areas, using a systematic approach. 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 high- and 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.
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