Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention—results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial

Author:

Traka Maria H1ORCID,Melchini Antonietta1,Coode-Bate Jack12,Al Kadhi Omar12,Saha Shikha1ORCID,Defernez Marianne1ORCID,Troncoso-Rey Perla1ORCID,Kibblewhite Helen1ORCID,O'Neill Carmel M1ORCID,Bernuzzi Federico1,Mythen Laura1,Hughes Jackie1ORCID,Needs Paul W1ORCID,Dainty Jack R3,Savva George M1ORCID,Mills Robert D2,Ball Richard Y4ORCID,Cooper Colin S3,Mithen Richard F15

Affiliation:

1. Quadram Institute Bioscience, Norwich, United Kingdom

2. Department of Urology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom

3. Norwich Medical School, University of East Anglia, Norwich, United Kingdom

4. Norfolk and Waveney Cellular Pathology Service, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom

5. Liggins Institute, University of Auckland, New Zealand

Abstract

ABSTRACT Background Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. Objective We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. Methods Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and dietary assessment at the start and end of the study. Patients received a weekly 300 mL portion of soup made from a standard broccoli (control) or from 1 of 2 experimental broccoli genotypes with enhanced concentrations of glucoraphanin, delivering 3 and 7 times that of the control, respectively. Gene expression in tissues from each patient obtained before and after the dietary intervention was quantified by RNA sequencing followed by gene set enrichment analyses. Results In the control arm, there were several hundred changes in gene expression in nonneoplastic tissue during the 12 mo. These were associated with an increase in expression of potentially oncogenic pathways including inflammation processes and epithelial–mesenchymal transition. Changes in gene expression and associated oncogenic pathways were attenuated in men on the glucoraphanin-rich broccoli soup in a dose-dependent manner. Although the study was not powered to assess clinical progression, an inverse association between consumption of cruciferous vegetables and cancer progression was observed. Conclusion Consuming glucoraphanin-rich broccoli soup affected gene expression in the prostate of men on active surveillance, consistent with a reduction in the risk of cancer progression. This trial was registered at clinicaltrials.gov as NCT01950143.

Funder

Prostate Cancer Foundation

Biotechnology and Biological Sciences Research Council

Publisher

Oxford University Press (OUP)

Subject

Nutrition and Dietetics,Medicine (miscellaneous)

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