The only gastric cancer (GC) syndrome with a proven inherited defect is designated as hereditary diffuse gastric cancer (HDGC) and is caused by germline E-cadherin/CDH1 alterations.
Carriers of CDH1 mutations are at risk for a highly penetrant, aggressive and early-onset diffuse-type gastric cancer, and these individuals are usually offered prophylactic total gastrectomy.
An overview of the various pathways of importance in gastric cancer, as discovered through in-vitro, primary cancer and mouse model studies, is presented and the clinical importance of CDH1 mutations is discussed.
The results revealed that CDH1, cyclooxygenase-2 and matrix metalloproteinase genes had significantly higher expression levels, whereas the expression levels of dermatopontin and transforming growth factor β receptor 2 were decreased in GC samples.
In meta-analysis, CDH1 -160C>A showed an inverse association with GC among Asians (OR, 0.76; 95% CI, 0.55-1.05) and a positive association among Caucasians (OR, 1.40; 95% CI, 0.95-2.04).
The E-cadherin promoter frequently undergoes hypermethylation in human gastric cancers, particularly those of the undifferentiated-scattered histologic subtype.
CDH1 hypermethylation status was found to be associated with advancement of disease, distant organ metastases and lymph node invasion in Gastric cancer patients.
Germline mutations in the E-cadherin gene (CHD1) have been described that result in the development of diffuse hereditary gastric cancer in young patients.