Gastric cancer (GC) is considered to be one of the leading cancers in East Asians, and mutations in the CDH1 gene and the reduced expression of E-cadherin are the most frequent genetic alterations in gastric cancer.
In this perspective, we investigated whether hypermethylation in the CDH1 promoter region is correlated with poor prognosis of patients with surgically resected, node-positive, diffuse gastric cancer.
Germline inactivation of the E-cadherin gene (CDH1) is associated with hereditary diffuse gastric cancer (HDGC), a rare autosomal dominant syndrome predisposing to both diffuse gastric cancer (DGC) and lobular breast cancer (LBC).
Thirty-six percent (5 of 14) of the families with a documented DGC diagnosed before the age of 50 and other cases of gastric cancer carried CDH1 germ line mutations.
Heterozygotes with the CDH1 mutation have a 70-80% chance of developing gastric cancer and once patients have invasive, symptomatic disease there is a high associated morbidity and mortality.
The risk of development of gastric cancer is high in families affected b-y these syndromes, but only hereditary diffuse gastric cancer is genetically explained (caused by germline alterations of CDH1, which encodes E-cadherin).
In conclusion, our results indicated that plasma CDH1 levels may serve as a risk marker against gastric cancer and variant genotypes of rs26160 and rs17690554 may contribute to the etiology of diffuse gastric cancer in this study.
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.
In this report, we describe a germline CDH1 c.48 G>C variant found in a 21 year old woman and her living great uncle, who were both diagnosed with gastric cancer and belong to a family with high incidence of this type of cancer.
Germline truncating CDH1 mutations are found in 48% of families with multiple cases of gastric cancer and at least one documented case of DGC in an individual under 50 years of age.