CDH1 gene encodes for a protein called cadherin-1 or E-cadherin. E-cadherin is a member of the cadherin family of proteins, which is found on the surface of cells that help neighboring cells adhere to each other and form organized tissues. E-cadherin is a specific calcium ion-dependent cell adhesion molecule that is involved in transmitting chemical signals within cells, controlling cellular movement, and regulating the activity of certain genes. E-cadherin is also a tumor suppressor gene that prevents cells from growing and dividing in an uncontrolled way to form cancerous cells.
Mutations in this gene have been identified in different types of cancers, such as hereditary diffuse gastric cancer, endometrial cancer, and ovarian cancer. In addition, women who have mutations in the CDH1 gene have a high risk of developing breast cancer in the milk-producing glands (lobular breast cancer). Studies have also shown that cancer patients with CDH1 hypermethylation have higher survival rate than those without hypermethylation.
Lynch et al. (2011) studied a preliminary pedigree of four individuals from a single family with gastric cancer. All four individuals tested positive for a c.1137G>A mutations in the CDH1 gene. A family information service was then conducted where 40 family members gathered and were provided with proper counseling. Twenty-three family members have been tested for CDH1; 13 were positive and 10 were negative. The proband, a CDH1 mutation carrier, has undergone successful prophylactic total gastrectomy.
Al-Moundhri et al. (2010a) sequenced the CDH1 gene among Omanis to investigate the association between CDH1 polymorphisms and gastric cancer (GC) risk. Four CDH1 polymorphisms were analyzed: +54 T>C, -160 C>A, -616 G>C, and -3159 T>C. The -160 -AA genotype was found to be associated with increasing the risk of GC among Omanis, while no association was found between the other polymorphisms and GC risk. Haplotype analysis for the four polymorphisms revealed that the OR of CCGC was 1.5, and that of CAGC was 1.5, but did not reach a statistical significance. Simultaneously, Al-Moundhri et al. (2010b) investigated the association between global and specific DNA methylation levels and clinicopathological features among 105 Omani patients with gastric cancer. Using PCR and pyrosequencing, five CpG methylation sites were measured in the CDH1 gene. An association was found between older age and CDH1 promoter hypermethylation at sites 3, 5 and on average across the five CDH1 sites. In addition, there was an association between male gender and CDH1 promoter hypermethylation at sites 2, 3, 4 and 5.