Folate and Epigenetics: Colorectal Cancer Risk and Detection

  • Nancy Lévesque
  • Daniel Leclerc
  • Rima RozenEmail author
Reference work entry


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.


Biomarker Carcinogenesis Colorectal cancer DNA damage Folic acid Genetic polymorphism Methylation MTHFR SEPT9 

List of Abbreviations


Betaine homocysteine S-methyltransferase


Body mass index


CpG island methylator phenotype


Colorectal cancer






Deoxythymidine monophosphate


Deoxyuridine monophosphate


Familial adenomatous polyposis


Guaiac-based fecal occult blood test


Hereditary nonpolyposis colorectal cancer


Immunological-based fecal occult blood test


Methionine adenosyltransferase 1A


Methylenetetrahydrofolate dehydrogenase-cyclohydrolase-formyltetrahydrofolate synthetase 1


Methylenetetrahydrofolate reductase


5-Methyltetrahydrofolate-homocysteine methyltransferase


5-Methyltetrahydrofolate-homocysteine methyltransferase reductase






Serine hydroxymethyltransferase 1




Thymidylate synthetase


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Departments of Human Genetics and PediatricsMcGill University, The Research Institute of the McGill University Health CentreMontrealCanada

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