Carcinogenesis Advance Access published online on July 22, 2004
Carcinogenesis, doi:10.1093/carcin/bgh241
© 2004 by Oxford University Press
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1 Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands
* To whom correspondence should be addressed. E-mail: j.vandelft{at}grat.unimaas.nl.
The evidence from epidemiological and experimental studies that vegetables reduce the risk of colorectal cancer is convincing. However, the involved genes and genetic pathways are not clear. The aim of this study was to identify genes that are modulated in vivo in colorectal mucosa by vegetables, and to investigate whether colon adenoma patients respond differently compared to healthy controls. Twenty female adenoma patients and eight healthy controls were randomly split into two groups of ten and four persons respectively, receiving either a 50% decreased (= 75 g/day) or doubled (= 300 g/day) intake of vegetables for two weeks. In order to assess effects on gene expression at target level, colorectal biopsies were collected before and after the intervention. Total RNA was isolated from the biopsies to measure gene expression of 597 genes relevant for responses to xenobiotics by microarray technology, followed by confidence analyses to identify differentially expressed genes. Mainly genes related to cell cycle control and genes for oxidoreductase activities were over-represented in the list of modulated genes. Twenty genes were modulated which are known to be related to (colon)carcinogenesis. Seven genes were similarly modulated in patients and controls, for example fos proto-oncogene and ornithine decarboxylase. Thirteen genes were modulated differently in patients compared to controls, including cyclooxygenase-2 and Human mdm2-A in patients and cytochrome P45027B1, -2C19, -2D6, -2C9, and -3A4 in controls. Almost all the effects on modulating the expression of genes by altering vegetable intake can be mechanistically linked to cellular processes that explain either prevention of colorectal cancer risk by high vegetable intake or increased colorectal cancer risk by low vegetable intake. Furthermore, it seems that vegetables in patients affect genes involved in late stage of colorectal cancer, whereas in controls genes involved in the initiation phase are modulated.
Revised July 1, 2004
Accepted July 18, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Altered vegetable intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls
2 Department of Gastroenterology, Maasland Hospital Sittard, Sittard, The Netherlands
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