Journal Article

Altered vegetable intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls

Simone G.J. van Breda, Ebienus van Agen, Leopold G.J.B. Engels, Edwin J.C. Moonen, Jos C.S. Kleinjans and Joost H.M. van Delft

in Carcinogenesis

Volume 25, issue 11, pages 2207-2216
Published in print November 2004 | ISSN: 0143-3334
Published online November 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh241
Altered vegetable intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls

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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 with 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 2 weeks. In order to assess the effects on gene expression at the 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 with 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 the late stage of colorectal cancer, whereas in controls genes involved in the initiation phase are modulated.

Keywords: AFP, alpha-fetoprotein; AMACR, methyl-CoA racemase alpha; APC, adenomatous polyposis coli; ATF3, activating transcription factor 3; CCNA2, cyclin A2; CCNG1, cyclin G1; CDK, cyclin-dependent protein kinases; C-FOS, fos proto-oncogene; CHK1, checkpoint kinase-1; COX-2, cyclooxygenase-2; CRC, colorectal cancer; CYP2C9, cytochrome P450 2C9; CYP2C19, cytochrome P450 2C19; CYP2D6, cytochrome P450 2D6; CYP3A4, cytochrome P450 3A4; CYP27B1, cytochrome P450 27B1; MDM2, human mdm2-A; ODC1, ornithine decarboxylase 1; PKCB1, protein kinase C beta 1; PRDX1, peroxiredoxin 1; PTGS2, prostaglandin-endoperoxide synthase 2

Journal Article.  6363 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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