Abstract PL04-03: Folate and cancer: Is timing everything?

Folate is an essential B vitamin utilized for one‐carbon transfer reactions, including those related to the methylation of DNA and nucleotide synthesis. Epidemiologic and experimental studies show that a low‐folate status is associated with an increased risk of colorectal neoplasia. However, the actions of folate in cancer prevention appear to be modulated by both genetic susceptibility and timing with respect to carcinogenic progression. Functional polymorphisms in genes encoding several key enzymes in folate metabolism have been linked to cancer risk and exemplify the importance of nutrigenetic interactions in this biologic pathway. Yet, perhaps more importantly, the timing of folate administration during carcinogenesis may also impact the outcome and result in opposing effects: A higher folate status is expected to protect against mutations and, thus, may reduce the progression from normal tissue to pre‐malignant lesions; however, a higher folate status may subsequently enhance the growth of pre‐malignant lesions or any existing tumors, due to the supporting role of folate in the provision of nucleotides for DNA synthesis. Data from clinical trials suggest potential increases in risk of colorectal polyps and prostate cancer in folic acid intervention arms. Mathematical models from our group suggest that supplementation early in life could be beneficial, but adversely affect cancer rates later in life. These influences appear predominantly driven by effects on thymidylate synthesis. Because at this point available data are incomplete, prior to making recommendations, investigation is needed of the effects of folate supplementation among cancer patients, who are at risk of recurrence, as well as among individuals with cancer precursors.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL04-03.