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Folate and Epigenetics: Colorectal Cancer Risk and Detection

  • Nancy Lévesque
  • Daniel Leclerc
  • Rima Rozen
Reference work entry

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.

Keywords

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

List of 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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Copyright information

© 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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