Height, obesity, and the risk of TMPRSS2:ERG-defined prostate cancer

Rebecca E. Graff, Thomas U. Ahearn, Andreas Pettersson, Ericka M. Ebot, Travis Gerke, Kathryn L. Penney, Kathryn M. Wilson, Sarah C. Markt, Claire H. Pernar, Amparo G. Gonzalez-Feliciano, Mingyang Song, Rosina T. Lis, Daniel R. Schmidt, Matthew G. Vander Heiden, Michelangelo Fiorentino, Edward L. Giovannucci, Massimo Loda, Lorelei A. Mucci


Background: The largest molecular subtype of primary prostate cancer is defined by the TMPRSS2:ERG gene fusion. Few studies, however, have investigated etiologic differences by TMPRSS2:ERG status. Because the fusion is hormone-regulated and a man’s hormonal milieu varies by height and obesity status, we hypothesized that both may be differentially associated with risk of TMPRSS2:ERG-defined disease.

Methods: Our study included 49,372 men from the prospective Health Professionals Follow-up Study. Participants reported height and weight at baseline in 1986 and updated weight biennially thereafter through 2009. Tumor ERG protein expression (a TMPRSS2:ERG marker) was immunohistochemically assessed. We used multivariable competing risks models to calculate HRs and 95% confidence intervals (CIs) for the risk of ERG-positive and ERG-negative prostate cancer.

Results: During 23 years of follow-up, we identified 5,847 incident prostate cancers, among which 913 were ERG-assayed. Taller height was associated with an increased risk of ERG-positive disease only [per 5 inches HR 1.24; 95% confidence interval (CI), 1.03–1.50; Pheterogeneity = 0.07]. Higher body mass index (BMI) at baseline (per 5 kg/m2 HR 0.75; 95% CI, 0.61–0.91; Pheterogeneity = 0.02) and updated BMI over time (per 5 kg/m2 HR 0.86; 95% CI, 0.74–1.00; Pheterogeneity = 0.07) were associated with a reduced risk of ERG-positive disease only.

Conclusions: Our results indicate that anthropometrics may be uniquely associated with TMPRSS2:ERG-positive prostate cancer; taller height may be associated with greater risk, whereas obesity may be associated with lower risk.

Impact: Our study provides strong rationale for further investigations of other prostate cancer risk factors that may be distinctly associated with subtypes.

Published In Cancer Epidemiology, Biomarkers & Prevention
Date Feb 1, 2018
DOI 10.1158/1055-9965.EPI-17-0547


Graff RE, Ahearn TU, Pettersson A, Ebot EM, Gerke TA, Penney KL, Wilson KM, Markt S, Pernar CH, Gonzalez-Feliciano AG, Song M, Lis R, Schmidt DR, Vander Heiden MG, Fiorentino M, Giovannucci EL, Loda M, Mucci LA. Height, obesity, and the risk of TMPRSS2:ERG-defined prostate cancer. Cancer Epidemiol Biomarkers Prev 2018; 27(2): 193--200. PMID: 29167279 PMCID: PMC5809280.