Abstract B045: Gene expression pathways associated with vigorous physical activity in prostate cancer

Abstract

Listen

Translate article

Abstract Background: Epidemiologic studies have consistently shown that men engaged in high levels of physical activity have lower risks of advanced and fatal prostate cancer. The mechanisms underlying this association are not well understood but may include changes in hormonal and anti-inflammatory pathways. Our objective was to investigate the link between prediagnostic physical activity and gene expression alterations in prostate tumor and adjacent normal tissue. Methods: We performed whole-gene expression profiling on tumor (N=248) and adjacent normal tissue (N=117) among a subset of men diagnosed with indolent and lethal prostate cancer between 1986 and 2005 in the prospective Health Professionals Follow-up Study. Men were followed prospectively for prostate cancer outcomes through 2011. Physical activity was ascertained by self-report of the average number of hours per week spent engaged in various forms of recreational physical activity at baseline and every two years thereafter. We examined cumulative average physical activity of vigorous intensity in units of metabolic equivalent of task (MET)-hours/week updated from baseline to the time prostate cancer diagnosis. Gene set enrichment analysis was performed among KEGG and hallmark gene sets to identify pathways with differential expression by vigorous activity. Results: We identified 33 KEGG and four Hallmark gene sets enriched in the adjacent normal tissue comparing men in the highest compared to the lowest quintile of vigorous activity (false-discovery rate < 0.25). Among the significant gene sets identified were cancer-related pathways as well as vascular smooth muscle contraction, angiogenesis, and insulin-signaling pathways. No gene sets were significantly enriched in the tumor tissue. Conclusions: These findings suggest that physical activity may influence prostate cancer development through epigenetic alterations in the prostate tissue. Future studies are needed to confirm these findings and further investigate potential mechanisms linking physical activity to risk of lethal prostate cancer. Citation Format: Claire H. Pernar, Giovanni Parmigiani, Edward L. Giovannucci, Eric B. Rimm, Stephen Finn, Michelangelo Fiorentino, Ericka M. Ebot, Lorelei A. Mucci. Gene expression pathways associated with vigorous physical activity in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B045.