Mismatch Repair Genes Hmlh1 And Hmsh2 And Gastrointestinal Tumors Genetic Susceptibility

AIMS: to investigate single nucleotide polymorphisms in mismatch repair gene hMSH2 , hMLHl and the genetic susceptibility to gastrointestinal cancers. METHODS: A case-control study has been taken on subjects including 45 sporadic colorectal ,82 sporadic gastric, 71 familial gastric cancers and 147 health controls. Genomic DNA was extracted from peripheral blood of all subjects. The polymorphisms were detected by a PCR-based DHPLC analysis and verified by DNA sequencing. RESULTS: The polymorphism IVS1+9C -G in hMSH2 gene was detected in 42/126 healthy individuals, 29/72 sporadic gastric, 31/71 familial gastric cancers and 21/45 sporadic colorectal cancers. The polymorphism V384D in hMLHl gene was in 9/147 healthy individuals, 10/82 sporadic gastric and 5/41 sporadic colorectal cancers. For hMLHl gene V384D polymorphism, significant difference exists between colorectal cancer patients or gastric cancer patients and controls, especially between lower age patients and controls.. As for IVS+9C-G in hMSH2 gene ,significantly different also exist between sporadic gastric cancers at young age( < 50 yrs) and health controls(P<0.05), but not in sporadic colorectal cancers. No significant difference is found between familial gastric cancers and controls. Further statistics based on histological type of sporadic gastric cancers reveals that the frequency of IVS+9CG polymorphism is higher in poorly differentiated-type cancers than in differentiated cancers (P < 0.01) .CONCLUSION: The genetic polymorphisms of V384D in hMLHl gene and IVS1+9C-G in hMSH2 gene may play a role in the onset in gastrointestinal cancers , especially in cancers at lower age. Determination of these polymorphisms may be suitable to identify individuals with high risk of gastric and colorectal cancer.