Relative distribution of folate species is associated with global DNA methylation in human colorectal mucosa

Liu, Jia, Hesson, Luke B., Meagher, Alan P., Bourke, Michael J., Hawkins, Nicholas J., Rand, Keith N., Molloy, Peter L., Pimanda, John E. and Ward, Robyn L. (2012) Relative distribution of folate species is associated with global DNA methylation in human colorectal mucosa. Cancer Prevention Research, 5 7: 921-929. doi:10.1158/1940-6207.CAPR-11-0577


Author Liu, Jia
Hesson, Luke B.
Meagher, Alan P.
Bourke, Michael J.
Hawkins, Nicholas J.
Rand, Keith N.
Molloy, Peter L.
Pimanda, John E.
Ward, Robyn L.
Title Relative distribution of folate species is associated with global DNA methylation in human colorectal mucosa
Journal name Cancer Prevention Research   Check publisher's open access policy
ISSN 1940-6207
1940-6215
Publication date 2012-07
Sub-type Article (original research)
DOI 10.1158/1940-6207.CAPR-11-0577
Open Access Status Not Open Access
Volume 5
Issue 7
Start page 921
End page 929
Total pages 9
Place of publication Philadelphia, PA United States
Publisher American Association for Cancer Research
Language eng
Abstract Folate exists as functionally diverse species within cells. Although folate deficiency may contribute toDNA hypomethylation in colorectal cancer, findings on the association between total folate concentration and global DNA methylation have been inconsistent. This study determined global, LINE-1, and Alu DNA methylation in blood and colon of healthy and colorectal cancer patients and their relationship to folate distribution. Blood and normal mucosa from 112 colorectal cancer patients and 114 healthy people were analyzed for global DNA methylation and folate species distribution using liquid chromatography tandem mass spectrometry. Repeat element methylation was determined using end-specific PCR. Colorectal mucosa had lower global and repeat element DNA methylation compared with peripheral blood (P < 0.0001). After adjusting for age, sex and smoking history, global but not repeat element methylation was marginally higher in normal mucosa from colorectal cancer patients compared with healthy individuals. Colorectal mucosa from colorectal cancer subjects had lower 5-methyltetrahydrofolate and higher tetrahydrofolate and formyltetrahydrofolate levels than blood from the same individual. Blood folate levels should not be used as a surrogate for the levels in colorectal mucosa because there are marked differences in folate species distribution between the two tissues. Similarly, repeat element methylation is not a good surrogate measure of global DNA methylation in both blood and colonic mucosa. There was no evidence that mucosal global DNA methylation or folate distribution was related to the presence of cancer per se, suggesting that if abnormalities exist, they are confined to individual cells rather than the entire colon.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Office of the Vice-Chancellor
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