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ALDH1L1 and ALDH1L2 Folate Regulatory Enzymes in Cancer

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Alcohol and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1032))

Abstract

Epidemiological studies implicate excess ethanol ingestion as a risk factor for several cancers and support the concept of a synergistic effect of chronic alcohol consumption and folate deficiency on carcinogenesis. Alcohol consumption affects folate-related genes and enzymes including two major folate-metabolizing enzymes, ALDH1L1 and ALDH1L2. ALDH1L1 (cytosolic 10-formyltetrahydrofolate dehydrogenase) is a regulatory enzyme in folate metabolism that controls the overall flux of one-carbon groups in folate-dependent biosynthetic pathways. It is strongly and ubiquitously down-regulated in malignant tumors via promoter methylation, and recent studies underscored this enzyme as a candidate tumor suppressor and potential marker of aggressive cancers. A related enzyme, ALDH1L2, is the mitochondrial homolog of ALDH1L1 encoded by a separate gene. In contrast to its cytosolic counterpart, ALDH1L2 is expressed in malignant tumors and cancer cell lines and was implicated in metastasis regulation. This review discusses the link between folate and cancer, modifying effects of alcohol consumption on folate-associated carcinogenesis, and putative roles of ALDH1L1 and ALDH1L2 in this process.

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Authors and Affiliations

  1. Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA

    Sergey A. Krupenko & Natalia I. Krupenko

  2. UNC Nutrition Research Institute, Chapel Hill, NC, USA

    Sergey A. Krupenko & Natalia I. Krupenko

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  1. Sergey A. Krupenko
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  2. Natalia I. Krupenko
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Correspondence to Sergey A. Krupenko .

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Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the US, Washington, DC, USA

    Samir Zakhari

  3. Mishra Laboratory, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Lopa Mishra

  4. Salem Medical Centre, University of Heidelberg, Heidelberg, Baden-Württemberg, Germany

    Helmut K. Seitz

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Krupenko, S.A., Krupenko, N.I. (2018). ALDH1L1 and ALDH1L2 Folate Regulatory Enzymes in Cancer. In: Vasiliou, V., Zakhari, S., Mishra, L., Seitz, H. (eds) Alcohol and Cancer. Advances in Experimental Medicine and Biology, vol 1032. Springer, Cham. https://doi.org/10.1007/978-3-319-98788-0_10

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