Abstract:  To investigate the role of DNA promoter demethylation of cancer-related antigen gene ( CAGE ), melanoma antigen gene A1 ( MAGE-A1 ), and melanoma antigen gene A3 ( MAGE-A3 ) in early carcinogenesis and advanced-stage gastric carcinoma. Methods: A total of 87 fresh samples were collected from patients who underwent gastric endoscopy. The samples were divided into three groups based on pathological results, namely, gastric carcinoma, premalignant lesions, and normal control. Demethylation of CAGE, MAGE-A1, and MAGE-A3 promoter areas in each group was determined using the methylation-specific polymerase chain reaction. Results: The positive rates of demethylation of the three genes in the gastric carcinoma, premalignant lesion, and normal control groups, were as follows: CAGE: 80.0% ( 24/30 ), 37.5% ( 12/32 ), and 4.0% ( 1/25 ), respectively; MAGE-A1: 60.0% ( 18/30 ), 21.9% ( 7/32 ), respectively, and 0 ( 0/25 ); and MAGE-A3: 46.7% ( 14/30 ), 12.5% ( 4/32 ), and 8% ( 2/25 ), respectively. Hypomethylation of CAGE, MAGE-A1, and MAGE-A3 promoter areas significantly decreased one by one from gastric carcinoma to premalignant lesion to normal mucosa. There was statistical significance when the three genes were compared among the three groups ( P < 0.05 ). Of the 30 cases with gastric carcinoma, hypomethylation of at least one gene promoter area occurred in 27 cases, at least two gene promoters were found in 23, and all three gene promoters were found in 7. Conclusion: Changes in the demethylation of CAGE, MAGE-A1, and MAGE-A3 promoter areas may occur in the early stage of carcinogenesis. This process plays a role in the occurrence and progression of gastric cancer. The combined detection for the demethylation of a gene promoter may enhance the efficiency of detecting hypomethylation in gastric cancer.