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Crit Rev Oncol Hematol. 2005 Jul;55(1):13-36.

Folate and its preventive potential in colorectal carcinogenesis. How strong is the biological and epidemiological evidence?

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Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.


Based on a 15-year old hypothesis, it is believed that an adequate ingestion of folate vitamins decreases, whereas a nutritional depletion of folate increases the risk of colorectal cancer. The present article reviews the efforts to provide biochemical and epidemiological evidence for folate as a chemopreventive agent against colorectal carcinogenesis. BIOLOGICAL EVIDENCE: Tetrahydrofolates govern the intracellular one-carbon metabolism and account for proper DNA biosynthesis and macromolecular modification. Numerous experimental studies traced different molecular pathways and tried to link folate depletion with DNA instability and/or mutagenesis. However, none of the proposed underlying molecular mechanisms appear clearly defined. EPIDEMIOLOGICAL EVIDENCE: Numerous case-control and prospective studies have been conducted on folate and colorectal cancer, which all together miss a clinical bottom line. The recommendation of folate intake to prevent colorectal cancer is therefore not evidence-based.

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