Eat Your Broccoli!

In a recent paper by Traka et al the authors state:

These findings suggest that consuming broccoli interacts with GSTM1 genotype to result in complex changes to signalling pathways associated with inflammation and carcinogenesis in the prostate. We propose that these changes may be mediated through the chemical interaction of isothiocyanates with signalling peptides in the plasma. This study provides, for the first time, experimental evidence obtained in humans to support observational studies that diets rich in cruciferous vegetables may reduce the risk of prostate cancer and other chronic disease.

As NCBI states:

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. 

 GSTM1 is a significant factor in many cancers, especially melanoma. They conclude:

First, we demonstrate that routine prostate needle biopsies can be used for global gene expression analyses in addition to histological assessment, and that it is possible to monitor changes in  expression with time. It is notable that men within both dietary arms of the study had significant changes in the androgen receptor pathway.

 It is possible that these changes in androgen signalling are associated with aging and independent of diets, or they may have been induced by a common component of both the broccoli-rich and pea-rich diet. 

To our knowledge there is no data on the rate of change on androgen signalling in men of this age with HGPIN. This observation suggests further study is warranted. Analysis of the rate of change of gene expression of men diagnosed with either HGPIN or localized prostate cancer through sequential biopsies may provide reliable biomarkers to measure the likelihood of both carcinogenesis and progression to aggressive cancer, and complement
histological examination of needle biopsies and measurement of plasma PSA levels. 

Secondly, stratification of global gene expression profiles by genotype has been informative, and this approach could be extended to other genes to dissect patterns of gene expression in prostate or other tissues.

 Lastly, it is conceivable that other dietary phytochemicals, such as polyphenolic derivatives, could also chemically interact with signalling peptides in the plasma, in a similar manner to the suggested mechanism of action of isothiocyanates.

This is an interesting study especially from the perspective of following the gene trail as well as understanding the detailed chemistry related to its control. We have examined HGPIN in some detail and it has been argued elsewhere that it is a necessary precursor of PCa. However we have also noted that in certain men with HGPIN, after an high density number of cores in a prostate biopsy, 24 or more, that the HGPIN regresses to the point that none can be observed on subsequent exams.

This paper may be of use not only in understanding the nature of phytogenic control but also for remission.

Reference

Traka, M., et al, Broccoli Consumption Interacts with GSTM1 to Perturb Oncogenic Signalling Pathways in the Prostate, PLOS, July 2008, Volume 3, Issue 7

NCBI, http://www.ncbi.nlm.nih.gov/gene/2944