The Glu346Lys polymorphism and frameshift mutations of the Methyl-CpG Binding Domain 4 gene in gastrointestinal cancer.

MBD4 (Methyl-CpG Binding Domain 4) is a human DNA repair protein that may be involved in DNA mismatch repair. The polymorphisms and frameshift mutations in MBD4 may influence cancer susceptibility and the development of cancer. The specific aim of this study was to investigate whether frameshift mutations of the MBD4 gene and the codon 346 polymorphism were associated with microsatellite instability (MSI) and the risk for gastrointestinal cancer. We examined the MSI, frameshift mutations and polymorphisms of the MBD4 gene in 84 patients with gastric cancers, 82 colorectal cancers and 299 healthy controls. MSI was found in 19 (22.6%) and 26 (31.7%) of the gastric and colorectal cancer samples, respectively. The mutation analysis revealed no frameshift mutations in the MBD4 gene among the gastrointestinal cancers. The frequencies of genotypes: Glu/Glu, Glu/Lys and Lys/Lys were 41.7% (35/84), 41.7% (35/84) and 16.6% (14/84), respectively, in the gastric cancer cases, and 42.7% (35/82), 36.6% (30/82) and 20.7% (17/82), respectively, in the colorectal cancers. MSI was not associated with the MBD4 codon 346 polymorphism and there was no significant difference in the frequency of the genotypes between healthy controls and gastric cancer patients (P=0.2748). However, the MBD4 codon 346 polymorphism was significantly associated with the risk of colorectal cancer (P=0.0315). Our findings suggest that microsatellite instability may not be associated with frameshift mutations in the MBD4 gene, and that the MBD4 codon 346 polymorphism may play arole in colorectal cancer susceptibility in the Korean population.