Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal cancer in a Chinese population

Epidemiologic, structural, and bioinformatic analyses were used to evaluate variants in the MSH2 and MLH1 genes in 187 subjects with suspected hereditary gastrointestinal cancer in China. An increased frequency of variants was observed in exon 7 of the MSH2 gene; there was a statistical difference (P < 0.05) between the colorectal cancer (CRC) group (6/82, or 7.32%) or the gastric cancer (GC) group (8/105, or 7.62%) and the controls (1/112, or 0.89%). The odds ratio (OR) was 8.76 for CRC and 9.15 for GC, suggesting an association between the presence of variants in exon 7 of the MSH2 gene and risk of gastrointestinal cancer in the studied population. In addition, MSH2 1168T showed trends toward association with CRC and GC in young (<50 yr) sporadic disease patients (OR = 10.97 and 17.15, respectively). The c.1168C>T (p.Leu390Phe), c.1255C>A (p.Gln419Lys), and c.1261C>A (p.Leu421Met) in exon 7 and c.518T>G (p.Leu173Arg) in exon 3 of MSH2 were suspected as predisposing to gastrointestinal cancer. Variants c.505A>G (p.Ile169Val), c.1221C>G (p.Leu407Leu) and c.1223A>G (p.Tyr408Cys) in MSH2 and c.655 A>G (p.Ile219 Val) and c.927C>T (p.Pro309Pro) in MLH1 might be merely polymorphisms. Consequences of the variant c.2101C>A (p.Gln701Lys) in MLH1 remain to be elucidated.