Relationship of plasma folic acid and status of DNA methylation in human gastric cancer

To evaluate the anti-cancer effects of folic acid at the molecular level, we determined plasma folic acid concentration by radioimmuno-assay and the degree of total genomic DNA methylation by incubating DNA with H-3-S-adenosylmethionine (H-3-SAM) in the presence of a methylase, and analyzed the methylation status of the c-myc and c-Ha-ras oncogenes by Southern blotting in 21 patients with advanced gastric cancer. The degree of total genomic DNA methylation of cancerous tissues was significantly lower than that of paracancerous and non-cancerous tissues; c-myc and c-Ha-ras oncogenes from cancerous (10/21, 5/10) and paracancerous (13/21, 4/10) tissues were hypomethylated. The plasma folic acid concentration in patients who showed hypomethylation was lower than that patients showing normal methylation. These findings suggest that a decrease in folic acid, and the subsequent DNA hypomethylation, may be involved in human gastric carcinogenesis.