Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans

Abstract

Objectives: This study reports the influence of colorectal neoplasia on methylation intermediates and folate concentrations in human colonic mucosa, as well as systemic measures of folate status, to examine biomarkers and possible mechanisms of folate-related carcinogenesis.

Subjects: A total of 47 patients were selected from those previously diagnosed with adenocarcinoma of the colorectum undergoing surgery. For each individual, we obtained a biopsy of the adenocarcinoma and a biopsy of normal appearing mucosa, to perform an intra-individual comparison.

Results: The 'methylation' ratio (S-adenosylmethionine/S-adenosylhomocysteine (SAH)) was lower in pathological tissue vs normal mucosa (P=0.08), mainly due to a much higher SAH concentration (P<0.005). Colonic folate concentration was significantly diminished in malignant tissue (P<0.0001). Plasma homocysteine concentration was within the normal to high range, and folate and vitamin B12 plasma concentrations were within the low to normal range as compared with normative values.

Conclusion: Our results contribute to the hypothesis that altered DNA methylation and methyl metabolism is associated with colorectal neoplasia.