Pre-diagnostic circulating sex hormone levels and risk of prostate cancer by ERG tumour protein expression.

Rebecca E Graff, Allison Meisner, Thomas U Ahearn, Michelangelo Fiorentino, Massimo Loda, Edward L Giovannucci, Lorelei A Mucci, Andreas Pettersson

Journal: British journal of cancer 2016;114(8):939-44

PMID: 26986253

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Abstract

BACKGROUND

Experimental studies have shown androgen receptor stimulation to facilitate formation of the TMPRSS2:ERG gene fusion in prostate cell lines. No study has tested whether higher pre-diagnostic circulating sex hormone levels in men increase risk of developing TMPRSS2:ERG-positive prostate cancer specifically.

METHODS

We conducted a nested case-control study of 200 prostate cancer cases and 1057 controls from the Physicians' Health Study and Health Professionals Follow-up Study. We examined associations between pre-diagnostic circulating levels of total testosterone, free testosterone, DHT, androstanediol glucuronide, estradiol, and SHBG and risk of prostate cancer by TMPRSS2:ERG status. TMPRSS2:ERG was estimated by ERG immunohistochemistry. We used multivariable unconditional polytomous logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of ERG-positive (n=94) and, separately, ERG-negative (n=106) disease.

RESULTS

Free testosterone was significantly associated with the risk of ERG-positive prostate cancer (OR: 1.37, 95% CI: 1.05-1.77), but not ERG-negative prostate cancer (OR: 1.09, 95% CI: 0.86-1.38) (Pdiff=0.17). None of the remaining hormones evaluated showed clear differential associations with ERG-positive vs ERG-negative disease.

CONCLUSIONS

These findings provide some suggestive evidence that higher pre-diagnostic free testosterone levels are associated with an increased risk of developing TMPRSS2:ERG-positive prostate cancer.

Address: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.; Department of Epidemiology & Biostatistics, University of California San Francisco, 1450 3rd Street, San Francisco, CA 94158, USA.; Department of Biostatistics, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA.; Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA.; Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Via Pietro Albertoni, 15, 40138 Bologna, Italy.; Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.; Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

DOI: 10.1038/bjc.2016.61

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https://doi.org/10.1038/bjc.2016.61

MeSH Terms: Case-Control Studies, Estradiol, Follow-Up Studies, Gonadal Steroid Hormones, Humans, Immunohistochemistry, Logistic Models, Male, Middle Aged, Odds Ratio, Prospective Studies, Prostatic Neoplasms, Receptors, Androgen, Risk, Serine Endopeptidases, Testosterone, Trans-Activators, Transcriptional Regulator ERG