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Folate and Epigenetics: Colorectal Cancer Risk and Detection

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Handbook of Nutrition, Diet, and Epigenetics

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Abstract

Colorectal cancer (CRC) is the fourth leading cause of cancer deaths worldwide. Initiation and development of colorectal tumors result from the accumulation of genetic and epigenetic alterations in colonic epithelial cells, causing their ultimate transformation into malignant adenocarcinomas. Increasing evidence points toward diet as a major environmental contributor to CRC risk. Several studies have reported that adequate folate intake may confer a protective effect for CRC risk. However, the increase in folate intake in many populations has led to some concerns about potential deleterious effects with respect to tumor growth, but thus far there have been no consistent reports of increased CRC risk due to folate supplementation. Nonetheless, animal studies have suggested a modulatory effect of folate intake depending on the timing of carcinogenesis. Genetic polymorphisms in folate one-carbon metabolism can also influence CRC risk. In addition to genetic variation, epigenetic changes, including alterations in DNA methylation, have been extensively studied in CRC and shown to occur at early stages of tumorigenesis. Consequently, DNA methylation changes could be potential biomarkers for CRC and may be useful for early diagnosis, personalized therapy, or prognosis. Some promising blood-based epigenetic biomarkers have been reported, but additional investigation is required for improvement of sensitivity and specificity.

Nancy Lévesque and Daniel Leclerc contributed equally to this work.

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Abbreviations

BHMT1:

Betaine homocysteine S-methyltransferase

BMI:

Body mass index

CIMP:

CpG island methylator phenotype

CRC:

Colorectal cancer

DMG:

Dimethylglycine

DMH:

Dimethylhydrazine

dTMP:

Deoxythymidine monophosphate

dUMP:

Deoxyuridine monophosphate

FAP:

Familial adenomatous polyposis

gFOBT:

Guaiac-based fecal occult blood test

HNPCC:

Hereditary nonpolyposis colorectal cancer

iFOBT:

Immunological-based fecal occult blood test

MAT1A:

Methionine adenosyltransferase 1A

MTHFD1:

Methylenetetrahydrofolate dehydrogenase-cyclohydrolase-formyltetrahydrofolate synthetase 1

MTHFR:

Methylenetetrahydrofolate reductase

MTR:

5-Methyltetrahydrofolate-homocysteine methyltransferase

MTRR:

5-Methyltetrahydrofolate-homocysteine methyltransferase reductase

SAH:

S-Adenosylhomocysteine

SAM:

S-Adenosylmethionine

SHMT1:

Serine hydroxymethyltransferase 1

THF:

Tetrahydrofolate

TYMS:

Thymidylate synthetase

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    Authors and Affiliations

    1. Departments of Human Genetics and Pediatrics, McGill University, The Research Institute of the McGill University Health Centre, 1001 Décarie Blvd., Bloc E, Rm E M0.3211, Montreal, QC, H4A 3J1, Canada

      Nancy Lévesque, Daniel Leclerc & Rima Rozen

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    1. Nancy Lévesque
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    2. Daniel Leclerc
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    3. Rima Rozen
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    Correspondence to Rima Rozen .

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    1. c/o Editorial Board 978-0-387-78665 , Heidelberg, Baden-Württemberg, Germany

      Vinood Patel

    2. Kings College , London, United Kingdom

      Victor Preedy

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    Lévesque, N., Leclerc, D., Rozen, R. (2017). Folate and Epigenetics: Colorectal Cancer Risk and Detection. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-31143-2_93-1

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    • DOI: https://doi.org/10.1007/978-3-319-31143-2_93-1

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