Study On The Gene Variations And The Susceptibility Of Gastrointestinal Cancers

【Objective】The gastrointestinal cancers are most frequent malignancy in China. Several different genes have been identified in gastric and colorectal cancers. Mutations in these genes result in a marked predisposition to gastrointestinal cancers. Study is performed to open out the genetic background of the Chinese individuals suffering from the gastrointestinal cancers,to find out the characters of the mutations in those genes,to make it possible of gene diagnosis and supervision for the individuals with predisposition to gastrointestinal cancers.【Methods】Genomic DNA was extracted from peripheral blood lymphocytes of 22 FAP and 35 colorectal cancers accordant to Bethesda criteria, and from normal/tumor colorectal tissues of 76 sporadic colorectal cancers. hMLH1, hMSH2, APC and MYH genes were screened for mutations with systematic analysis techniques including DHPLC, PTT, multiple PCR-HPLC, MLPA and DNA sequencing. Genomic DNA was extracted from peripheral blood lymphocytes of 105 gastric cancers (54 inherent patients with typical familial history of gastric cancer, 43 patients with young age or nontypical familial history of cancer and 8 sporadic gastric cancers. hMLH1, hMSH2, and MYH genes were screened for mutations with DHPLC and DNA sequencing.【Results】Most of the 34 patients showing MSI+ in 76 sporadic colorectal cancers were young. Nine germline missense mutations and three large fragment deletions in hMLH1 or hMSH2 genes were found in 35 colorectal cancers accordant to Bethesda criteria and 34 sporadic colorectal cancers showing MSI+. The frequency of mutations in exon 7 of hMSH2 gene in colorectal cancers is much higher than that in normal persons. Most of the mutations in exon 7 of hMSH2 gene are Leu390Phe. In sporadic colorectal cancers, the frequency of mutations in exon 7 of hMSH2 gene in young patients is much higher than that in...