Impaired methionine and folate metabolism in colorectal carcinogenesis

Epidemiological and experimental studies suggest that folate may modulate colorectal carcinogenesis. Its role could be associated with the importance of tetrahydrofolate in DNA and RNA methylation, as well as in thymidylate and purine synthesis, essential for DNA synthesis and repair. In consequence, we analyzed the global DNA methylation and S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) colonic mucosa concentration in biopsies with polyps vs. control biopsies from the same patients (n=45). Significant colonic DNA global hypomethylation (p < 0.05) was found in injured tissue vs. control. Moreover, a lower 'methylation' ratio (SAM:SAH) was observed in pathological tissue (3.69 +/- 0.38) vs. control (5.00 +/- 0.63), due to a much higher SAH concentration (12.03 +/- 1.36 vs. 5.45 +/- 0.49 nmol/g).