AIM:To give a comprehensive report of E-cadheringene (CDH1) variations in a population at a high risk for gastric cancer (GC).METHODS:The samples consisted of 178 men and 58 women with a mean age of 62.3 ± 9.4 years and an age range of 30-84 years.A total of 240 cancerfree controls were recruited (mean age of 61.8 ± 10.1 years,age range of 26-82 years).Samples were screened for CDH1 germline mutations by high-resolution melting analysis or directly sequencing.Luciferase reporter assay,RNA splicing assay and bioinformatic analysis were used to evaluate the effect of mutations.RESULTS:Four novel CDH1 sequence alterations were identified in GC patients including a G>T transition 49 bp before the start codon;a three-nucleotide deletion,c.44_46del TGC;one missense mutation,c.604G>A (V202I);and one variation in the intron,c.1320+7A>G.In addition,polymorphism frequencies were observed for CDH1-164delT,-161C>A,-73A>C,c.48+6C>T,c.48+62_48+63delinsCGTGCCCCAGCCC,c.894C>T (A298A),c.1224G>A (A408A),c.1888C>G (L630V),c.2076T>C (A692A),and c.2253C>T (N751N) which is similar to the data reported in http://www.ncbi.nlm.nih.gov/projects/SNP/.RNA splicing analysis suggested that the c.1320+7A>G and c.1224G>A variations did not affect exon splicing ability.Luciferase reporter assay demonstrated that the c.-49T variation might be helpful for E-cadherin transcription,though the increase in transcription activity is limited (only 33%).SIFT score and PolyPhen analysis both demonstrated that the L630V missense mutation probably damages protein function,while the V202I variant does not.CONCLUSION:This study reveals novel mutations in sporadic GC patients which had been poorly investigated for susceptibility genes. AIM: To give a comprehensive report of E-cadherin gene (CDH1) variations in a population at a high risk for gastric cancer (GC) .METHODS: The samples consisted of 178 men and 58 women with a mean age of 62.3 ± 9.4 years and an age range of 30-84 years. A total of 240 cancerfree controls were recruited (mean age of 61.8 ± 10.1 years, age range of 26-82 years). Samples were screened for CDH1 germline mutations by high-resolution melting analysis or directly sequencing. Luciferase assay were used to evaluate the effect of mutations .RESULTS: Four novel CDH1 sequence alterations were identified in GC patients including a G> T transition 49 bp before the start codon; a three-nucleotide deletion, c.44_46del TGC; one missense mutation, c.604G> A (V202I); and one variation in the intron, c.1320 + 7A> G. In addition, polymorphism frequencies were observed for CDH1-164delT, -161C> A, -73A> C, c.48 + 6C> T, c.48 + 62_48 + 63delinsCGTGCCCCAGCCC, c.894C> T (A298A), c.1224G> A A), c.1888C> G (L630V), c.2076T> C (A692A), and c.2253C> T (N751N) which is similar to the data reported in http: //www.ncbi.nlm.nih. gov / projects / SNP / .RNA splicing analysis suggested that the c.1320 + 7A> G and c.1224G> A variations did not affect exon splicing ability. Luciferase reporter assay that the c.-49T variation might be helpful for E -cadherin transcription, though the increase in transcription activity is limited (only 33%). SIFT score and PolyPhen analysis both demonstrated that the L630V missense mutation probably damages protein function, while the V202I variant does not. CONCLUSION: This study reveals novel mutations in sporadic GC patients which had been poorly investigated for susceptibility genes.