Abstract 5317: Association of physical activity with risk of prostate cancer defined by TMPRSS2:ERG
Authors: Pernar Claire H. , Ebot Ericka M. , Pettersson Andreas , Graff Rebecca E. , Ahearn Thomas U. , Gonzalez-Feliciano Amparo G. , Markt Sarah C. , Wilson Kathryn M. , Finn Stephen , Fiorentino Michelangelo , Giovannucci Edward L. , Mucci Lorelei A. 
Published: July 2017

Abstract
Background
There is growing evidence of heterogeneity in risk factor associations for prostate cancer defined by clinical and molecular characteristics. Physical activity has moderate protective effects on development of prostate cancer, in particular of advanced and fatal disease. We hypothesized that the influence of physical activity on hormonal and anti-inflammatory pathways may differentially affect the development of TMPRSS2:ERG-positive compared to TMPRSS2:ERG-negative tumors. Our objective was to examine the association between physical activity and risk of prostate cancer defined by the TMPRSS2:ERG fusion.
Materials & Methods
We followed 49,160 men in the prospective Health Professionals Follow-up Study from 1986 to 2010. Participants were age 40 years or older, had no previous cancer diagnosis, and reported physical activity by questionnaire. Men self-reported the average number of hours per week spent engaged in various forms of recreational physical activity at baseline and every two years thereafter with greater than 90% follow-up rates. We examined long-term physical activity type and intensity in units of metabolic equivalent of task (MET)-hours per week. Presence of the TMPRSS2:ERG fusion in tumor tissue was estimated by ERG protein expression using immunohistochemistry. We used competing risks models to obtain subtype-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of fusion-positive and fusion-negative prostate cancer.
Results
During 23 years of follow-up, 5,819 men were diagnosed with prostate cancer. Of the 2,389 men who underwent radical prostatectomy, 910 were assayed for ERG. Men with higher cumulative average vigorous activity had a lower risk of developing TMPRSS2:ERG-positive prostate cancer (top vs. bottom quintile multivariate HR: 0.64, 95% CI: 0.46-0.90, P-value for trend=0.01). There was no significant association observed between vigorous activity and risk of TMPRSS2:ERG-negative prostate cancer (HR: 0.93, 95% CI: 0.67-1.28, P-value for trend=0.46). However, the test for heterogeneity in these associations was not significant (P-value for heterogeneity=0.55). No association was observed between total activity and risk of either TMPRSS2:ERG subtype.
Conclusions
Physical activity of vigorous intensity is inversely associated with risk of TMPRSS2:ERG-positive but not TMPRSS2:ERG-negative prostate cancer. These findings suggest that regular vigorous activity may lower risk of prostate cancer through mechanisms specific to development of this fusion in prostate tumors. Future studies are needed to further elucidate these mechanisms and translate these findings into recommendations for prostate cancer prevention.
Citation Format: Claire H. Pernar, Ericka M. Ebot, Andreas Pettersson, Rebecca E. Graff, Thomas U. Ahearn, Amparo G. Gonzalez-Feliciano, Sarah C. Markt, Kathryn M. Wilson, Stephen Finn, Michelangelo Fiorentino, Edward L. Giovannucci, Lorelei A. Mucci. Association of physical activity with risk of prostate cancer defined by TMPRSS2:ERG [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5317. doi:10.1158/1538-7445.AM2017-5317