Physical activity and prostate gene expression in men with low-risk prostate cancer

Abstract

Purpose: Vigorous physical activity after diagnosis of localized prostate cancer may reduce the risk of disease progression and prostate cancer-specific mortality. The molecular mechanisms by which physical activity may exert protective effects in the prostate remain unknown.

Methods: We examined the associations between self-reported physical activity and gene expression patterns in morphologically normal prostate tissue of 71 men with low-risk prostate cancer on active surveillance. Differential gene expression, gene set, and pathway analyses were conducted comparing dichotomous groups defined by type, intensity, and amount of physical activity reported.

Results: Cell cycling and DNA repair pathways were up-regulated in men who participated in ≥ 3 h/week vigorous activity compared with men who did not. In addition, canonical pathways involved in cell signaling and metabolism, the cellular effects of sildenafil (Viagra), and the Nrf2-mediated oxidative stress response were modulated in men who reported ≥ 3 h/week of vigorous activity. Differential expression analysis at the individual gene level revealed modest differences between men who performed vigorous activity for ≥ 3 h/week and those who did not. There were no differences in prostate gene expression in comparisons with exercise groupings that did not consider both duration and intensity of activity.

Conclusions: Prostate gene expression and pathway analyses revealed sets of transcripts that may be modulated in normal prostate tissue by participating in ≥ 3 h/week of vigorous activity after diagnosis of low-risk prostate cancer. These findings suggest potential biological mechanisms by which vigorous activity may reduce risk of prostate cancer progression and warrant further study and validation.

Trial registration: ClinicalTrials.gov NCT00402285.

Figures

Figure 1. Differential expression analysis

Heatmap showing up-regulated (red) genes (upper right quadrant) and down-regulated (green) genes (lower right quadrant) in normal prostate of 71 men with low-risk prostate cancer who participated in ≥3 h/wk vigorous activity compared to men who engaged in