Somatic mutations of the
mitochondrial DNA (
mtDNA) are associated with development of various types of human
cancer. To elucidate the significance of somatic mutations of the
mtDNA in gastric
carcinogenesis, we examined
mtDNA mutations in
gastric cancers and in Helicobacter pylori-associated chronic
gastritis (H. pylori-CG), which is associated with an increased risk for
gastric cancer development. Specimens of
gastric cancer and gastric mucosa were obtained from 73
gastric cancer patients with H. pylori-CG, 75
cancer-free H. pylori-CG patients and 30 H. pylori-negative healthy subjects. Mutations of a specific mononucleotide repeat (D310) of the
mtDNA were examined by microsatellite assay.
mtDNA mutations were detected in 9 of 56 (16%)
gastric cancers, in 10 of 148 (7%) H. pylori-CG and none of the 30 H. pylori-negative healthy subjects.
mtDNA mutations in H. pylori-CG were significantly more frequent in
gastric cancer patients than in
cancer-free patients (12% vs. 1%, p=0.008). In addition,
mtDNA mutations in H. pylori-CG were significantly more frequent in patients with
mtDNA mutated
gastric cancer than in patients with
mtDNA unmutated
gastric cancer (66% vs. 4%, p<0.001). These data suggest that somatic mutations of the
mtDNA may be involved in the early stages of gastric
carcinogenesis.