Study of CDH1 germline mutation in hereditary diffuse gastric cancer and lobular breast cancer: a multicenter study in Iran

Mutations occurring in the CDH1 gene elevate the susceptibility to the development of hereditary diffuse gastric cancer (HDGC) as well as lobular breast cancer (LBC). LBCs with CDH1 germline mutations are classified as hereditary breast cancers, devoid of any indication of gastric carcinoma. As prophylactic gastrectomy is a recommended course of treatment for individuals with CDH1 mutations, it is advised that genetic testing be conducted for those who meet the criteria established by the National Comprehensive Cancer Network (NCCN). This study aimed to screen patients with HDGC for CDH1 testing and clinical management for the prevention of HDGC. Moreover, patients with LBC are tested for CDH1 mutation.

In this multicenter study, thirty-one patients with HDGC were selected among 615 patients and admitted for CDH1 mutation testing. PCR for all 16 exons of CDH1 and Sanger sequencing were performed. Patients with LBC who are negative for BRCA1/2 were also included in this study regardless of gastric cancer history.

The results showed that 5.04% of patients with DGC were identified as HDGC of which 9.6% of individuals had a pathogenic CDH1 mutation and only 15.38% of cases with a family history carried germline mutation in CDH1. Furthermore, 7.6% of patients with LBC and negative for a family history of gastric cancer have CDH1 mutation.

All patients who met the NCCN criteria were not CDH1 mutation-positive, indicating other genes should be involved in DGC. Moreover, patients with LBC and negative for BRCA1/2 are recommended for testing the mutation in CDH1.