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Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation.

ABSTRACT: Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n?=?29) or fish oil (n?=?27) supplementation or placebo (n?=?28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by these micronutrients.Global gene expression analysis revealed no significant individual genes that were associated with high intake of fish or tomato at baseline or after 3 months of supplementation with lycopene or fish oil. However, exploratory pathway analyses of rank-ordered genes (based on p-values not corrected for multiple comparisons) revealed the modulation of androgen and estrogen metabolism in men who routinely consumed more fish (p?=?0.029) and tomato (p?=?0.008) compared to men who ate less. In addition, modulation of arachidonic acid metabolism (p?=?0.01) was observed after 3 months of fish oil supplementation compared with the placebo group; and modulation of nuclear factor (erythroid derived-2) factor 2 or Nrf2-mediated oxidative stress response for either supplement versus placebo (fish oil: p?=?0.01, lycopene: p?=?0.001).We did not detect significant individual genes associated with dietary intake and supplementation of lycopene and fish oil. However, exploratory analyses revealed candidate in vivo pathways that may be modulated by these micronutrients.ClinicalTrials.gov NCT00402285.

SUBMITTER: Magbanua MJ

PROVIDER: S-EPMC3164676 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation.

Magbanua Mark Jesus M MJ Roy Ritu R Sosa Eduardo V EV Weinberg Vivian V Federman Scott S Mattie Michael D MD Hughes-Fulford Millie M Simko Jeff J Shinohara Katsuto K Haqq Christopher M CM Carroll Peter R PR Chan June M JM

PloS one 20110901 9

<h4>Background</h4>Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.<h4>Methods</h4>Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-mo ...[more]

PMID: 21912659

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Project description:Beneficial effects of long-chain omega-3 polyunsaturated fatty acids (n-3 FAs) are generally well-known from epidemiological studies, but the various mechanisms of action are not completely clarified. Regulation of gene expression is one known mechanism of action, but only very limited data of regulated pathways in humans after n-3 FA supplementation are available. Up to now, no studies compared gene expression changes after n-3 FA supplementation between normolipidemic and dyslipidemic subjects. Therefore, the aim of this study was to investigate the effects of n-3 FA administration on whole genome expression profiles in the blood of normo- and dyslipidemic subjects. We conducted an intervention study with normo- and dyslipidemic men aged between 29 and 51 years, which were subdivided into four groups with a balanced age distribution and randomized to either six fish oil capsules per day providing 1.5 g docosahexaenoic acid and 1.0 g eicosapentaenoic acid or corn oil capsules rich in linoleic acid per day for a period of 12 weeks. Venous blood samples were collected at baseline as well as after 4 hours, 1 week and 12 weeks of supplementation. For each investigation time point, the samples of each group were pooled together to minimize inter-individual variability. All subjects have successfully completed the study, but for the microarray experiments, nine subject samples were excluded. Therefore, the microarray experiments are based on the following group characteristics: normolipidemic fish oil group (FO-N): pool of nine RNAs from normolipidemic subjects supplemented with fish oil; normolipidemic corn oil group (CO-N): pool of six RNAs from normolipidemic subjects supplemented with corn oil; dyslipidemic corn oil group (CO-D): pool of eight RNAs from dyslipidemic subjects supplemented with corn oil; dyslipidemic fish oil group (FO-D): pool of nine RNAs from dyslipidemic subjects supplemented with fish oil. The twenty normolipidemic and the twenty dyslipidemic subjects were subdivided into two groups. Thus, a total of four groups with ten men per group passed through the study. To realize a comparable mean age between groups, the formation of groups was performed by stratified allocation according to subject's age. The four study groups were randomly assigned to different study products by an uninvolved collaborator. Subjects ingested either six FO or six corn oil (CO) capsules per day for a period of twelve weeks. The daily n-3 PUFA intake via FO capsules was 2.7 g (1.14 g DHA and 1.56 g EPA). The predominant FA of the CO capsules was the omega-6 (n-6) PUFA linoleic acid (LA, 18:2n-6). Thus, the daily LA intake via CO capsules was 3.05 g LA. The subjects were instructed to ingest the capsules together with food, three in the morning and three in the evening, and to maintain their usual exercise and dietary habits throughout the intervention time. As an exception, at the first intervention day, all six capsules were ingested at the same time in the morning after a standardised breakfast. During each visit, fasting blood samples were collected by venepuncture. Additionally, participants completed a questionnaire to obtain information about changes in medication, dietary (e.g., changes in weekly fish intake, preferred fish dishes or species, respectively) and lifestyle habits (e.g., physical activity), as well as the tolerability of the capsules. This record summarizes the results of 16 microarrays. The samples originate from whole blood of normo- and dyslipidemic subjects supplemented with either fish oil or corn oil for 4 h, 1 week and 12 weeks. Microarrays were hybridized in a loop design with one common reference using a dye-swap approach.

Dataset Information

Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation.

Publications

Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation.

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