British Journal of Nutrition

Short Communication

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

Simone G. J. van Bredaa1 c1, Joost H. M. van Delfta1, Leopold G. J. B. Engelsa2, Jos C. S. Kleinjansa1 and John C. Mathersa3

a1 Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands

a2 Department of Gastroenterology, Maasland Hospital Sittard, Sittard, The Netherlands

a3 Human Nutrition Research Centre, School of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK

Abstract

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 β 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 quantitative 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 1 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 1 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.

(Received March 31 2008)

(Revised July 22 2008)

(Accepted August 26 2008)

(Online publication September 25 2008)

Correspondence:

c1 Corresponding author: Dr Simone G. J. van Breda, fax +31 43 3884146, email s.vanbreda@grat.unimaas.nl

Footnotes

Abbreviations: C-FOS, fos proto-oncogene; CRC, colorectal cancer; MTHFR, 5,10-methylenetetrahydrofolate reductase; ODC1, ornithine decarboxylase 1; PKCB1, protein kinase C β 1