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Eur Urol. 2018 Oct 6. pii: S0302-2838(18)30730-9. doi: 10.1016/j.eururo.2018.09.041. [Epub ahead of print]

A Prospective Study of the Association between Physical Activity and Risk of Prostate Cancer Defined by Clinical Features and TMPRSS2:ERG.

Author information

1
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: cpernar@mail.harvard.edu.
2
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
3
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
4
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
5
Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy.
6
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
7
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
8
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
9
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
10
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
11
Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
12
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
13
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
14
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Histopathology, Trinity College, Dublin, Ireland.
15
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy; Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.

Abstract

BACKGROUND:

Growing evidence shows that clinical and molecular subtypes of prostate cancer (PCa) have specific risk factors. Observational studies suggest that physical activity may lower the risk of aggressive PCa. To our knowledge, the association between physical activity and PCa defined by TMPRSS2:ERG has not been evaluated.

OBJECTIVE:

To prospectively examine the association between physical activity and risk of PCa defined by clinical features and TMPRSS2:ERG.

DESIGN, SETTING, AND PARTICIPANTS:

We studied 49160 men aged 40-75 yr in the Health Professionals Follow-up Study from 1986 to 2012. Data was collected at baseline and every 2 yr with >90% follow-up. Total and vigorous physical activity were measured in metabolic equivalent of task (MET)-h/wk.

OUTCOME MEASURES AND STATISTICAL ANALYSIS:

Advanced PCa was defined as stage T3b, T4, N1, or M1 at diagnosis and lethal PCa as distant metastases or death due to disease over follow-up. Presence of TMPRSS2:ERG was estimated by immunohistochemistry of ERG protein expression. Cox proportional hazards models were used to obtain multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of subtype-specific PCa.

RESULTS AND LIMITATIONS:

During 26 yr of follow-up, 6411 developed PCa overall and 888 developed lethal disease. There were no significant associations between total physical activity and risk of PCa in the overall cohort. In multivariable-adjusted models, men in the highest quintile of vigorous activity had a significant 30% lower risk of advanced PCa (HR: 0.70, 95% CI: 0.53-0.92) and 25% lower risk of lethal PCa (HR: 0.75, 95% CI: 0.59-0.94) than men in the lowest quintile of vigorous activity. The association was independent of screening history. Vigorous activity was not associated with total PCa in the overall cohort but was inversely associated among highly screened men (top vs bottom quintile, HR: 0.83, 95% CI: 0.70-0.97). Of all cases, 945 were assayed for ERG (48% ERG-positive). Men with higher vigorous activity had a lower risk of ERG-positive PCa (top vs bottom quintile, HR: 0.71, 95% CI: 0.52-0.97). There was no significant association with the risk of ERG-negative disease (p heterogeneity=0.09).

CONCLUSIONS:

Our study confirms that vigorous physical activity is associated with lower risk of advanced and lethal PCa and provides novel evidence for a lower risk of TMPRSS2:ERG-positive disease.

PATIENT SUMMARY:

The identification of modifiable lifestyle factors for prevention of clinically important prostate cancer (PCa) is needed. In this report, we compared risk of PCa in men with different levels of physical activity. Men with higher vigorous activity had a lower risk of developing advanced and lethal PCa and PCa with the common TMPRSS2:ERG gene fusion.

KEYWORDS:

Exercise; Molecular biomarkers; Physical activity; Prevention; Prostate cancer

PMID:
30301696
PMCID:
PMC6451672
[Available on 2020-04-06]
DOI:
10.1016/j.eururo.2018.09.041

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