The study of family heredity of gastric cancer in china

Abstract

Objective To detect the protein expression, methylatian promoter,germ-line mutations of E-Cadherin gene (CDHI) in Eight kindreds of ICG-HGC according with Intemation Collaborative Group on Hereditary Gastric Cancer standard and 30 cases of gastric carcer with gastric cancer family history in China and to investigate their possible role. Methods Eight probands diagnozed with ICG-HGC criterion and 30 cases of gastric carcer with gastric cancer family history were enrolled in our database from 1994 to 2007. Tumor tissues were checked for CDH1 expression by immunohistochemistry (IHC). CDH1 DNA se-quencing was performed for all its 16 exons in blood or normal tissues of the same patients to detect germ-line mutations. Methylation promoter study was performed by using specific primers and PCR. Results IHC analysis confirmed CDH1 apparent downregulation in all ICG-HGC probands including seven CDH1 ex-pression negative and one downregulation, whereas 16 cases of patients with gastric cancer family history CDH1 expression negative. CDH1 promoter hypermethylation was found in 19 cases with gastric cancer family history and 6 probands with ICG-HGC. DNA sequencing revealed the presence of three silent muta-tions in two patients of 30 cases with gastric cancer family history in normal tissue, thereby excluding any germ-line cells mutations in eight ICG-HGC probands probands. Conclusion CDH1 gene germ-line muta-tions may be relatively rare or have some other hereditary predisposing genes in chinese hereditary gastric cancer. CDH1 promoter hypermethylation is the main cause to lead to downregulation/disassembly of CDH1 Expression. Key words: Gastric cancer; DNA mutations; E-cadherin; Methylation