Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.
Cancer Epidemiol Biomarkers Prev. 2021 Apr;30(4):751-756. doi: 10.1158/1055-9965.EPI-20-1461. Epub 2021 Jan 26.
Men engaged in high physical activity have lower risks of advanced and fatal prostate cancer. Mechanisms underlying this association are not well understood but may include systemic and tumor-specific effects. We investigated potential mechanisms linking physical activity and gene expression in prostate tissue from men with prostate cancer.
We included a subset of 118 men in the Health Professionals Follow-up Study diagnosed with prostate cancer between 1986 and 2005 with whole-transcriptome gene expression profiling on tumor and adjacent normal prostate tissue and physical activity data. Long-term vigorous physical activity was self-reported as the average time spent engaged in various forms of recreational physical activity at baseline and biennially until prostate cancer diagnosis. Gene set enrichment analysis was performed among KEGG and Hallmark gene sets to identify pathways with differential expression based on vigorous physical activity.
In adjacent normal tissue, we identified 25 KEGG gene sets enriched (downregulated) in the highest compared with lowest quintile of vigorous physical activity at an FDR <0.10, including a number of cancer- and immune-related pathways. Although no gene sets reached statistical significance in tumor tissue, top gene sets differentially expressed included TGF beta, apoptosis, and p53 signaling pathways.
These findings suggest that physical activity may influence the tumor microenvironment. Future studies are needed to confirm these findings and further investigate potential mechanisms linking physical activity to lethal prostate cancer.
Identification of gene expression alterations in the prostate associated with physical activity can improve our understanding of prostate cancer etiology.
从事高强度体力活动的男性患晚期和致命前列腺癌的风险较低。虽然这种关联的机制尚不清楚，但可能包括系统性和肿瘤特异性影响。我们研究了与男性前列腺癌组织中体力活动和基因表达相关的潜在机制。
我们纳入了 118 名男性，他们参加了健康专业人员随访研究，这些男性在 1986 年至 2005 年间被诊断患有前列腺癌，并且对肿瘤和相邻正常前列腺组织进行了全转录组基因表达谱分析，并获得了体力活动数据。长期剧烈体力活动是根据基线和每两年一次的自我报告，评估男性从事各种形式的娱乐性体力活动的平均时间。根据剧烈体力活动进行基因集富集分析，以确定基于 KEGG 和 Hallmark 基因集的差异表达途径。
在相邻的正常组织中，我们在最高五分位数和最低五分位数的剧烈体力活动之间鉴定出了 25 个 KEGG 基因集（下调），其中包括许多癌症和免疫相关途径。尽管在肿瘤组织中没有基因集达到统计学意义，但差异表达的顶级基因集包括 TGF beta、凋亡和 p53 信号通路。
这些发现表明体力活动可能影响肿瘤微环境。需要进一步的研究来确认这些发现，并进一步研究体力活动与致命前列腺癌之间的潜在机制。
确定与体力活动相关的前列腺基因表达改变可以提高我们对前列腺癌病因的理解。
