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.
This case highlights the importance of recognition of the HDGC syndrome and of testing for CDH1 germline mutations in young individuals with diffuse gastric cancer without a family history of the disease.
No truncating or splice site CDH1 mutations were identified by PCR single-strand conformational polymorphism in these families or in eight individual patients who had both prostate and gastric cancer.
In this study, we systematically reviewed the studies of CDH1 hypermethylation and GC, and evaluated the association between CDH1 hypermethylation and GC using meta-analysis methods.
Participants included one 37-year-old man with multiple polyps in his stomach and a family history of stomach cancer, one 18 year-old man with a confirmed CDH1 mutation and a family history of stomach cancer, and one 33-year-old man with confirmed metastatic gastric adenocarcinoma.
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.
CDH1a, a non-canonical transcript of the CDH1 gene, has been found to be expressed in some gastric cancer (GC) cell lines, whereas it is absent in normal gastric mucosa.
To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis.
Large meta-analyses confirmed the association between IL8, IL10, TNF-b, TP53 and PSCA, while genetic variation at different genes such as XPG, PLCE1, HFE, ERCC5, EZH2, DOC2, CYP19A1, ALDH2, and CDH1 have been reported to be associated with GC risk.
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.
Downregulation of E-cadherin (CDH1) plays a key role in the development of diffuse-type gastric cancer, and DNA methylation is a major cause of the gene's silencing.
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.