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Methylation status of CpG islands in the promoter region of genes differentially expressed in colonic mucosa from adenoma patients and controls in response to altered vegetable intake

Lookup NU author(s): Professor John Mathers



Vegetables may protect against colorectal cancer (CRC) via changes in gene expression involved in anticarcinogenic mechanisms. There is considerable evidence that aberrant DNA methylation plays an important role in carcinogenesis. Furthermore, DNA methylation can be affected by dietary components. Therefore, in the present study, we investigated the DNA methylation status of CpG dinucleotides within the promoter region of the four genes protein kinase C beta 1, ornithine decarboxylase 1, fos proto-oncogene and 5,10-methylenetetrahydrofolate reductase in the colon of female sporadic adenoma patients and healthy controls. These genes were chosen because their expression was modulated in response to altered vegetable intake, they are functionally relevant for CRC; they have CpG islands in their promoter region, and a methylation-specific restriction enzyme is available to permit quanlitative assay. No significant differences in extent of methylation in colon DNA were detected for any of the four genes in both adenoma polyp patients and healthy controls after altering vegetable intake. Interestingly, before the intervention, ornithine decarboxylase I promoter methylation was lower in the colonic mucosa of the adenoma polyp patients when compared with healthy control subjects, which may explain the increased ornithine decarboxylase I activity in CRC reported in the literature. In conclusion, we found no evidence that changes in promoter methylation were responsible for differences in expression of four genes in the human colonic mucosa in response to altered vegetable intake. The mechanism(s) responsible for this altered gene expression and, indeed, potential effects on methylation of other genes remain to be determined.

Publication metadata

Author(s): van Breda SGJ, van Delft JHM, Engels LGJB, Kleinjans JCS, Mathers JC

Publication type: Article

Publication status: Published

Journal: British Journal of Nutrition

Year: 2009

Volume: 101

Issue: 9

Pages: 1295-1299

Date deposited: 23/03/2011

ISSN (print): 0007-1145

ISSN (electronic): 1475-2662

Publisher: Cambridge University Press


DOI: 10.1017/S0007114508083529


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Funder referenceFunder name
European Commission's Research Directorate General
CT-2004-505944European Nutrigenomics Organization