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Journal of the National Cancer Institute Advance Access published online on August 8, 2007
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm105
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Published by Oxford University Press 2007.

EDITORIAL

One-Carbon Metabolism, Colorectal Carcinogenesis, Chemoprevention—with Caution

Regina G. Ziegler, Unhee Lim

Correspondence to: Regina G. Ziegler, PhD, MPH, Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Plaza South 8098, Bethesda, MD 20892-7246 (e-mail: zieglerr@mail.nih.gov).

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One-carbon metabolism comprises a network of integrated biochemical pathways that donate, and regenerate, the one-carbon moieties needed for physiologic processes. Efficient one-carbon metabolism is required for the biosynthesis of the purines, adenine and guanine, and the conversion of uridylate to thymidylate, which prevents the misincorporation of uracil into DNA (1). By donating a methyl group to homocysteine to create methionine, one-carbon metabolism also generates S-adenosylmethionine, the universal methyl donor, which is required for DNA methylation (1). Disruption of one-carbon metabolism can, therefore, interfere with DNA replication, DNA repair, and regulation of gene expression through methylation, each of which could promote carcinogenesis. One-carbon metabolism requires optimal activity of 25 or more enzymes, some of which depend on not only folate, a B vitamin, but also vitamins B-12, B-6, and B-2 (riboflavin) as coenzymes. Over the past . . . [Full Text of this Article]


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