Obesity and Prostate Cancer Risk According to Tumor TMPRSS2:ERG Gene Fusion Status

Am J Epidemiol. 2015 May 1;181(9):706-13. doi: 10.1093/aje/kwu344. Epub 2015 Apr 7.


The T2E gene fusion, formed by fusion of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific (ETS)-related gene (ERG), is found in approximately 50% of prostate cancers and may characterize distinct molecular subtypes of prostate cancer with different etiologies. We investigated the relationship between body mass index (BMI; weight (kg)/height (m)(2)) and prostate cancer risk by T2E status. Study participants were residents of King County, Washington, recruited for 2 population-based case-control studies conducted in 1993-1996 and 2002-2005. Tumor T2E status was determined for 563 prostate cancer patients who underwent radical prostatectomy. Information on weight, height, and covariables was obtained through in-person interviews. We performed polytomous logistic regression to calculate odds ratios and 95% confidence intervals for T2E-positive and -negative prostate cancer. Comparing the highest BMI quartile with the lowest, inverse associations were observed between recent (≥29.7 vs. <24.5: odds ratio = 0.66, 95% confidence interval: 0.45, 0.97) and maximum (≥31.8 vs. <25.9: odds ratio = 0.69, 95% confidence interval: 0.47, 1.02) BMI and the risk of T2E-positive prostate cancer. No significant associations were seen for men with T2E-negative tumors. This study provides evidence that obesity is specifically associated with reduced risk of developing androgen-responsive T2E fusion-positive tumors. The altered steroid hormone profile in obese men may contribute to this inverse association.

Keywords: TMPRSS2:ERG gene fusion; body mass index; obesity; prostate cancer.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Case-Control Studies
  • Humans
  • Male
  • Middle Aged
  • Obesity / complications*
  • Oncogene Fusion*
  • Prostatic Neoplasms / genetics*
  • Serine Endopeptidases / genetics*
  • Trans-Activators / genetics*
  • Transcriptional Regulator ERG


  • ERG protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Serine Endopeptidases
  • TMPRSS2 protein, human