Skip to main content
SpringerLink
Log in

Physical activity and prostate gene expression in men with low-risk prostate cancer

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Prostate (2012) SEER stat fact sheets. November 2011 SEER data submission: National Cancer Institute

  2. Dall’Era MA, Cooperberg MR, Chan JM et al (2008) Active surveillance for early-stage prostate cancer: review of the current literature. Cancer 112:1650–1659

    Article  PubMed  Google Scholar 

  3. Magbanua MJ, Roy R, Sosa EV et al (2011) Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation. PLoS ONE 6:e24004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Ornish D, Magbanua MJ, Weidner G et al (2008) Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proc Natl Acad Sci USA 105:8369–8374

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Chan JM, Weinberg V, Magbanua MJ et al (2011) Nutritional supplements, COX-2 and IGF-1 expression in men on active surveillance for prostate cancer. Cancer Causes Control 22:141–150

    Article  PubMed Central  PubMed  Google Scholar 

  6. Kenfield SA, Stampfer MJ, Giovannucci E, Chan JM (2011) Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol 29:726–732

    Article  PubMed Central  PubMed  Google Scholar 

  7. Richman EL, Kenfield SA, Stampfer MJ, Paciorek A, Carroll PR, Chan JM (2011) Physical activity after diagnosis and risk of prostate cancer progression: data from the cancer of the prostate strategic urologic research endeavor. Cancer Res 71:3889–3895

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Jones LW, Antonelli J, Masko EM et al (2012) Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer. J Appl Physiol 113:263–272

    Article  PubMed Central  PubMed  Google Scholar 

  9. Physical Activity Guidelines Advisory Committee (2008) Physical activity advisory committee report, 2008. Department of Health and Human Services, Washington

    Google Scholar 

  10. Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116–5121

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Dinu I, Potter JD, Mueller T et al (2007) Improving gene set analysis of microarray data by SAM-GS. BMC Bioinform 8:242

    Article  Google Scholar 

  12. Efron B, Tibshirani R (2007) On testing the significance of sets of genes. Ann Appl Stat 1:107–129

    Article  Google Scholar 

  13. Diehn M, Sherlock G, Binkley G et al (2003) SOURCE: a unified genomic resource of functional annotations, ontologies, and gene expression data. Nucleic Acids Res 31:219–223

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Subramanian A, Tamayo P, Mootha VK et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Stat Soc B Met 57:289–300

    Google Scholar 

  16. Radak Z, Naito H, Kaneko T et al (2002) Exercise training decreases DNA damage and increases DNA repair and resistance against oxidative stress of proteins in aged rat skeletal muscle. Pflugers Arch 445:273–278

    Article  CAS  PubMed  Google Scholar 

  17. Siu PM, Pei XM, Teng BT, Benzie IF, Ying M, Wong SH (2011) Habitual exercise increases resistance of lymphocytes to oxidant-induced DNA damage by upregulating expression of antioxidant and DNA repairing enzymes. Exp Physiol 96:889–906

    CAS  PubMed  Google Scholar 

  18. Rundle A (2005) Molecular epidemiology of physical activity and cancer. Cancer Epidemiol Biomark Prev 14:227–236

    Article  Google Scholar 

  19. La Vignera S, Condorelli R, Vicari E, D’Agata R, Calogero AE (2012) Physical activity and erectile dysfunction in middle-aged men. J Androl 33:154–161

    Article  PubMed  Google Scholar 

  20. Shamloul R, Ghanem H (2013) Erectile dysfunction. Lancet 381:153–165

    Article  CAS  PubMed  Google Scholar 

  21. Goeman JJ, Buhlmann P (2007) Analyzing gene expression data in terms of gene sets: methodological issues. Bioinformatics 23:980–987

    Article  CAS  PubMed  Google Scholar 

  22. Tian L, Greenberg SA, Kong SW, Altschuler J, Kohane IS, Park PJ (2005) Discovering statistically significant pathways in expression profiling studies. Proc Natl Acad Sci USA 102:13544–13549

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Strasser B, Steindorf K, Wiskemann J, Ulrich CM (2013) Impact of resistance training in cancer survivors: a meta-analysis. Med Sci Sports Exerc 45:2080–2090

    Google Scholar 

Download references

Acknowledgments

We thank the patients who participated in this study; Ritu Roy for providing assistance with preprocessing the raw gene expression data; Adam Olshen for the critical review of the manuscript; the Prostate Cancer Foundation; and the National Cancer Institute/National Institutes of Health for funding. NIH/NCI R01CA101042 and R25CA112355; Prostate Cancer Foundation.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA, USA

    Mark Jesus M. Magbanua

  2. Department of Epidemiology and Biostatistics, University of California San Francisco, 1450 3rd Street, San Francisco, CA, 94158-9001, USA

    Erin L. Richman & June M. Chan

  3. Department of Urology, University of California San Francisco, San Francisco, CA, USA

    Eduardo V. Sosa, Jeff Simko, Katsuto Shinohara, Christopher M. Haqq, Peter R. Carroll & June M. Chan

  4. Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

    Lee W. Jones

  5. Department of Pathology, University of California San Francisco, San Francisco, CA, USA

    Jeff Simko

  6. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA

    Peter R. Carroll & June M. Chan

  7. Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA

    Jeff Simko

Authors
  1. Mark Jesus M. Magbanua
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erin L. Richman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eduardo V. Sosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lee W. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeff Simko
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Katsuto Shinohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christopher M. Haqq
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter R. Carroll
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. June M. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to June M. Chan.

Additional information

Mark Jesus M. Magbanua and Erin L. Richman have contributed equally to this work.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magbanua, M.J.M., Richman, E.L., Sosa, E.V. et al. Physical activity and prostate gene expression in men with low-risk prostate cancer. Cancer Causes Control 25, 515–523 (2014). https://doi.org/10.1007/s10552-014-0354-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-014-0354-x

Keywords

Search

Navigation