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Cancer Causes & Control
Published in: Cancer Causes & Control 4/2010

01-04-2010 | Original paper

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

Authors: Bethany Van Guelpen, Anna M. Dahlin, Johan Hultdin, Vincy Eklöf, Ingegerd Johansson, Maria L. Henriksson, Inger Cullman, Göran Hallmans, Richard Palmqvist

Published in: Cancer Causes & Control | Issue 4/2010

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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.
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Metadata
Title
One-carbon metabolism and CpG island methylator phenotype status in incident colorectal cancer: a nested case–referent study
Authors
Bethany Van Guelpen
Anna M. Dahlin
Johan Hultdin
Vincy Eklöf
Ingegerd Johansson
Maria L. Henriksson
Inger Cullman
Göran Hallmans
Richard Palmqvist
Publication date
01-04-2010
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 4/2010
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-009-9484-y

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