Height, Obesity, and the Risk of TMPRSS2:ERG-Defined Prostate Cancer

Cancer Epidemiol Biomarkers Prev. 2018 Feb;27(2):193-200. doi: 10.1158/1055-9965.EPI-17-0547. Epub 2017 Nov 22.


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. Cancer Epidemiol Biomarkers Prev; 27(2); 193-200. ©2017 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Body Height
  • Body Mass Index
  • Body Weight
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Obesity / complications*
  • Oncogene Proteins, Fusion / analysis*
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Prospective Studies
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / etiology*
  • Prostatic Neoplasms / genetics
  • Risk Factors
  • Transcriptional Regulator ERG / analysis


  • ERG protein, human
  • Oncogene Proteins, Fusion
  • TMPRSS2-ERG fusion protein, human
  • Transcriptional Regulator ERG