Molecular Mechanisms of Dutasteride and Dietary Interventions to Prevent Prostate Cancer and Reduce Its Progression

• Effects of the Interventions on Lipid Metabolism From Blood and Prostatic Microenvironment [ Time Frame: 0-6-12 months ] [ Designated as safety issue: No ]
  In this aim the investigators will measure the effects of the interventions on the fatty acid profile of phospholipids from RBC and from snap frozen prostate tissue. Fatty acid profile from prostatic tissue has never been studied. The investigators aim that change in fatty acid intake will affect fatty acid profile of prostatic tissue. Fatty acid profile from red blood cells will serve as a marker of dietary fatty acid intake. Previous studies have shown that fatty acids profile from RBC differs from the one from muscle tissue and that the dietary effect on RBC fatty acids profile is almost maximal within 6 months.
  
  

• Effect of Interventions on Gene Expression Profile [ Time Frame: 0-6-12 months ] [ Designated as safety issue: No ]
  In this aim the investigators will investigate how the interventions affect prostate tissue gene expression profile determined by cDNA micro-array analysis. We hypothesize that a down-regulation will occur in genes associated with inflammation, androgen synthesis, cell proliferation and angiogenesis pathways. Also, this prospective study provides an opportunity of a retrospective comparison of baseline gene expression patterns from initial prostate biopsy will be correlated with baseline self-reported dietary intake.
  
  
• Effects of Interventions on Hormonal Metabolism [ Time Frame: 0-6-12 months ] [ Designated as safety issue: No ]
  The investigators will initially focus our attention on estrogens (Estrone, Estradiol) and most important androgens and their metabolites (dihydrotestosterone, testosterone, 3-α-diolglucuronide, androsterone glucuronide).
  
  
• Determine the Clinical Utility of Urine-Based Cancer Markers in the Context of Interventions to Reduce Cancer Progression [ Time Frame: 0-6-12 months ] [ Designated as safety issue: No ]
  Although one of the best tumor markers available to monitor disease recurrence after treatment, PSA lacks specificity to monitor patients on active surveillance. The expression of urinary PCA3 (developed in Québec) improves the diagnosis of prostate cancer over standard parameters, including PSA, and the PCA3 score was shown to correlate with grade, stage and tumor volume in prostatectomy specimen. Another gene-based marker, the TMPRSS2-ERG gene fusion transcript, is also associated with tumor aggressiveness and detected in urine.
  
  

The study has a duration of 1 year for each participant. Subjects will be first assigned to a dietary or a dutasteride intervention that they will consume for the first 6 months. After 6 months, all men will have a combined intervention of dutasteride and diet to complete follow-up of 12 months. This will allow us to study interactive effects.

Dietary intervention consists on a high w-3 long-chain fatty acids diet without supplement and to reduce intake of saturated and trans fatty acids.

Prostatic biopsies will be taken at time of diagnosis and at 6 and 12 months after the beginning of the study. Blood will be drawn before each prostate biopsy session and urine will be collected before each prostate biopsy and after digital rectal examination.