Cancer Causes & Control

, Volume 21, Issue 4, pp 557–566

One-carbon metabolism and CpG island methylator phenotype status in incident colorectal cancer: a nested case–referent study

  • Bethany Van Guelpen
  • Anna M. Dahlin
  • Johan Hultdin
  • Vincy Eklöf
  • Ingegerd Johansson
  • Maria L. Henriksson
  • Inger Cullman
  • Göran Hallmans
  • Richard Palmqvist
Original paper

DOI: 10.1007/s10552-009-9484-y

Cite this article as:
Van Guelpen, B., Dahlin, A.M., Hultdin, J. et al. Cancer Causes Control (2010) 21: 557. doi:10.1007/s10552-009-9484-y

Abstract

Objective

We related prediagnostic plasma folate, vitamin B12, and total homocysteine concentrations, and the MTHFR 677C>T and 1298A>C polymorphisms, to the risk of colorectal cancer with and without the CpG island methylator phenotype (CIMP).

Methods

This was a nested case–referent study of 190 cases and double, matched referents from the large, population-based Northern Sweden Health and Disease Study. Using archival tumor tissue, promoter methylation in an eight-gene panel was analyzed by MethyLight.

Results

A reduced risk of CIMP-low/CIMP-high CRC (≥1 gene methylated) was observed in subjects with very low plasma folate concentrations [multivariate odds ratio 2.96 (95% CI 1.24–7.08) for quintiles two to five versus one (lowest)]. With the exception of a reduced risk in MTHFR 677 TT-homozygotes, none of the other one-carbon variables were associated with the risk of CIMP-low/CIMP-high CRC. For CIMP-negative CRC, only the MTHFR polymorphisms were statistically significantly related to risk, inversely for 677C>T and positively for 1298A>C, but a tendency toward a reduced risk was observed in subjects with an adequate methyl availability, combining the plasma variables [multivariate odds ratio 0.61 (95% CI 0.32–1.15)].

Conclusion

Though limited by low power, these findings suggest the possibility of different roles for one-carbon metabolism in different pathways of colorectal tumorigenesis.

Keywords

DNA methylationFolateVitamin B12HomocysteineMTHFRColorectal cancer

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Bethany Van Guelpen
    • 1
  • Anna M. Dahlin
    • 1
  • Johan Hultdin
    • 2
  • Vincy Eklöf
    • 1
  • Ingegerd Johansson
    • 3
  • Maria L. Henriksson
    • 1
  • Inger Cullman
    • 4
  • Göran Hallmans
    • 5
  • Richard Palmqvist
    • 1
  1. 1.Department of Medical Biosciences, PathologyUmeå UniversityUmeåSweden
  2. 2.Department of Medical Biosciences, Clinical ChemistryUmeå UniversityUmeåSweden
  3. 3.Department of Odontology, CariologyUmeå UniversityUmeåSweden
  4. 4.Department of ChemistryUmeå UniversityUmeåSweden
  5. 5.Department of Public Health and Clinical Medicine, Nutrition ResearchUmeå UniversityUmeåSweden