Altered vegetable intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls.
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.
van Breda
Simone G J
SG
Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands.
van Agen
Ebienus
E
Engels
Leopold G J B
LG
Moonen
Edwin J C
EJ
Kleinjans
Jos C S
JC
van Delft
Joost H M
JH
D000236:Adenoma / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D003106:Colon / Q000166:cytology / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D018076:DNA, Complementary; D002149:Energy Intake; D005247:Feeding Behavior; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas; D012016:Reference Values; D014675:Vegetables
D018076:DNA, Complementary; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas