Abstract: BACKGROUND ＆ AIM: To detect the germline mutations in E_Cadherin gene (CDH1) and to investigate their possible role in familial gastric cancer. MATERIAL AND METHODS: With PCR, denaturing high_performance liquid chromatography (DHPLC) and direct sequencing, we screened all exons of the E_cadherin gene for mutations in 80 Chinese gastric cancer patients, 62 of whom had positive family history,we investigated 80 healthy individuals and conducted a case_control study to investigate whether such mutations affect the risk of developing gastric carcinoma. RESULTS: Two of 80 gastric cancer patients carried missense mutation Thr340Ala (heterozygosity). This variation was not found in the control population. We confirmed a T→C polymorphism site at position －13 in upstream of exon 13. The polymorphism was identified in 10 of 80 gastric cancer patients and 12 of 80 healthy individuals and the frequency of this polymorphism did not differ between the familial gastric cancer patients and controls. We found a germline E_cadherin nonsense mutation at codon 751 in exon 14 in 19 of 80 patients analyzed. Only 7 of 80 healthy individuals were Asn751Asn carriers, and significant difference existed between gastric cancer patients and control population, especially between the elder patients and controls. CONCLUSION: Though the germline mutations of CDH1 gene did not occur frequently in familial gastric cancer, CDH1 gene Asn751Asn single nucleotide polymorphism might increase the risk of gastric cancer in Chinese population.

Key words: familial gastric cancer, CDH1 gene, germline mutation