Consistent with this hypothesis, there was no evidence for induction of phase 2 gene transcription in the gastric mucosa after an acute broccoli intervention. In this study, we initially adopt an empirical approach in humans to elucidate the mechanisms that underlie the beneficial effects of a broccoli-rich diet, and explore the interaction with GSTM1. We compare and interpret global gene expression profiles in human prostate biopsy tissue before, during and after a 12 month broccoli-rich diet and a 12-month pea-rich diet. Subsequently, we provide a mechanistic explanation for how the observed changes in gene expression may be induced by normal dietary broccoli consumption. To our knowledge, this is the first dietary intervention study to analyse global gene expression profiles within a target tissue before and after a 12 month intervention, and to stratify gene expression profiles by genotype. While we do not observe any consistent changes in plasma PSA levels over the 12 month period of the intervention, we were able to quantify extensive changes in gene expression. We find little evidence to support potential mechanisms derived from animal and cell models to explain the observational data that consuming broccoli may Ginsenoside-F5 reduce risk of cancer, but considerable evidence for the perturbation of several signalling pathways that are associated with carcinogenesis and inflammation. It is possible that the net effect of perturbation of these pathways may reduce the risk of cell proliferation, and maintain cell and tissue homoeostasis. Dexrazoxane hydrochloride However, whilst quantification of gene expression and pathway analyses provides information concerning which pathways may be modified by time or diet, it can provide little information about the precise nature of how these pathways are perturbed. This requires further analysis of mRNA and protein turnover, and post translational protein modifications such as phosphorylation, associated with components of the signal transduction pathway and downstream targets. Furthermore, the effect of pathway perturbation may depend upon the precise cell type, with 
potentially differential effects occurring in epithelial and stromal cells. Despite these reservations, it is of considerable interest that broccoli intervention is associated with perturbation of TGFb1, EGF and insulin signalling, each of which has been associated with prostate carcinogenesis.