The association between MTHFR 677C > T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia

Joanna Hanks, Iyeman Ayed, Neil Kukreja, Chris Rogers, Jessica Harris, Alina Gheorghiu, Chee Ling Liu, Peter Emery, Maria Pufulete*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

19 Citations (Scopus)

Abstract

BACKGROUND: Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation.

OBJECTIVE: We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon.

DESIGN: We conducted a cross-sectional study of 336 men and women (age 19-92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively.

RESULTS: Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001).

CONCLUSION: MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia.

Original languageEnglish
Pages (from-to)1564-1574
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Volume98
Issue number6
DOIs
Publication statusPublished - Dec 2013

Structured keywords

  • BTC (Bristol Trials Centre)
  • Centre for Surgical Research

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biological Markers
  • Colon
  • Colorectal Neoplasms
  • Cross-Sectional Studies
  • DNA Methylation
  • Diet
  • Folic Acid
  • Folic Acid Deficiency
  • Genetic Association Studies
  • Great Britain
  • Humans
  • Intestinal Mucosa
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Middle Aged
  • Nutritional Status
  • Polymorphism, Single Nucleotide
  • Risk
  • Young Adult

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