For the first time, we evaluated by digital PCR the expression of CDH1 and CDH1a transcripts in cancer and normal tissue samples from 32 patients with intestinal-type gastric cancer.
Furthermore, the CDH1 c.1679C>G (p.T560R) variant segregated with gastric cancer in all three family members affected with gastric cancer in this family.
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).
Germline mutations in the E-cadherin gene (CHD1) have been described that result in the development of diffuse hereditary gastric cancer in young patients.
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.
HDGC, which is mainly caused by germline mutations in the E-cadherin gene (CDH1), renders a lifetime risk of gastric cancer of up to 70%, prompting a recommendation for prophylactic total gastrectomy.
Here we report the results of germline CDH1 mutation screening in 39 kindred with familial aggregation of gastric cancer, a subset of which fulfills the criteria defined by the IGCLC for HDGC.
Hereditary diffuse gastric cancer is caused by germline mutations in the epithelial cadherin (CDH1) gene and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer.
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.
However, three CDH1 polymorphisms in the same haplotype block, including the CDH1-160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers.
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.
In conclusion, this meta-analysis suggests that CDH1 -160 A-allele may play a protective role of stomach cancer development in Asians but not in Caucasians.
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).
In our area, in which a high rate of familial aggregation was demonstrated, the lack of germ line mutation of TP53 together with the infrequency of mutation of E-cadherin gene seem to limit the role of genetic predisposition in the development of gastric cancer.