Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA, USA.
Cancer Causes Control. 2014 Apr;25(4):515-23. doi: 10.1007/s10552-014-0354-x. Epub 2014 Feb 7.
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.
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.
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.
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.
在诊断为局限性前列腺癌后进行剧烈的身体活动可能会降低疾病进展和前列腺癌特异性死亡率的风险。身体活动可能通过何种分子机制对前列腺发挥保护作用尚不清楚。
我们研究了 71 名处于主动监测状态的低危前列腺癌男性的形态正常前列腺组织中自我报告的身体活动与基因表达模式之间的关联。通过报告的身体活动类型、强度和量来定义二分组,对差异基因表达、基因集和途径分析进行了比较。
与不进行剧烈活动的男性相比,每周进行≥3 小时剧烈活动的男性细胞周期和 DNA 修复途径上调。此外,报告每周进行≥3 小时剧烈活动的男性中,涉及细胞信号转导和代谢的经典途径、西地那非(伟哥)的细胞作用以及 Nrf2 介导的氧化应激反应受到调节。在个体基因水平上的差异表达分析显示,每周进行≥3 小时剧烈活动的男性与不进行剧烈活动的男性之间存在微小差异。与不考虑活动时间和强度的运动分组相比,在前列腺基因表达方面没有差异。
前列腺基因表达和途径分析显示,在诊断为低危前列腺癌后每周进行≥3 小时的剧烈活动可能会调节正常前列腺组织中的转录本集。这些发现提示了剧烈活动可能降低前列腺癌进展风险的潜在生物学机制,值得进一步研究和验证。