Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis

Susan J. Duthie

    Research output: Contribution to journalArticle

    165 Citations (Scopus)

    Abstract

    Inappropriate diet may contribute to one third of cancer deaths. Folates, a group of water-soluble B vitamins present in high concentrations in green, leafy vegetables, maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Folate deficiency has been implicated in the development of several cancers, including cancer of the colorectum, breast, ovary, pancreas, brain, lung and cervix. Generally, data from the majority of human studies suggest that people who habitually consume the highest level of folate, or with the highest blood folate concentrations, have a significantly reduced risk of developing colon polyps or cancer. However, an entirely protective role for folate against carcinogenesis has been questioned, and recent data indicate that an excessive intake of synthetic folic acid (from high-dose supplements or fortified foods) may increase human cancers by accelerating growth of precancerous lesions. Nonetheless, on balance, evidence from the majority of human studies indicates that dietary folate is genoprotective against colon cancer. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. This review presents recent evidence describing how these mechanisms act, and interact, to modify colon cancer risk.

    Original languageEnglish
    Pages (from-to)101-109
    Number of pages9
    JournalJournal of inherited metabolic disease
    Volume34
    Issue number1
    Early online date11 Jun 2010
    DOIs
    Publication statusPublished - Feb 2011

    Keywords

    • folic-acid deficiency
    • methylenetetrahydrofolate reductase polymorphism
    • randomized clinical-trial
    • hamster ovary cells
    • uracil misincorporation
    • colorectal-cancer
    • dietary-folate
    • common mutation
    • strand breaks
    • in-vitro

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