Modification of the Association Between Obesity and Lethal Prostate Cancer by TMPRSS2:ERG

• Published in: JNCI : Journal of the National Cancer Institute 2013-12, Vol.105 (24), p.1881-1890
• Main Authors: PETTERSSON, Andreas, LIS, Rosina T, NUTTALL, Elizabeth J, MARTIN, Neil E, SESSO, Howard D, POLLAK, Michael, STAMPFER, Meir J, KANTOFF, Philip W, GIOVANNUCCI, Edward L, LODA, Massimo, MUCCI, Lorelei A, MEISNER, Allison, FLAVIN, Richard, STACK, Edward C, FIORENTINO, Michelangelo, FINN, Stephen, GRAFF, Rebecca E, PENNEY, Kathryn L, RIDER, Jennifer R
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - analysis; Body Mass Index; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Health risk assessment; Hormones; Humans; Immunohistochemistry; Male; Medical prognosis; Medical sciences; Medicin och hälsovetenskap; Metabolic diseases; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Obesity; Obesity - complications; Odds Ratio; Oncogene Proteins, Fusion - analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prostate cancer; Prostatectomy - methods; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - etiology; Prostatic Neoplasms - mortality; Prostatic Neoplasms - surgery; Surveys and Questionnaires; Tumors; Up-Regulation; Waist Circumference
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djt332

TMPRSS2:ERG is a hormonally regulated gene fusion present in about half of prostate tumors. We investigated whether obesity, which deregulates several hormonal pathways, interacts with TMPRSS2:ERG to impact prostate cancer outcomes. The study included 1243 participants in the prospective Physicians' Health Study and Health Professionals Follow-Up Study diagnosed with prostate cancer between 1982 and 2005. ERG overexpression (a TMPRSS2:ERG marker) was assessed by immunohistochemistry of tumor tissue from radical prostatectomy or transurethral resection of the prostate. Body mass index (BMI) and waist circumference, measured on average 1.3 years and 5.3 years before diagnosis, respectively, were available from questionnaires. Data on BMI at baseline was also available. We used Cox regression to calculate hazard ratios and 95% confidence intervals (CIs). All statistical tests were two-sided. During a mean follow-up of 12.8 years, 119 men developed lethal disease (distant metastases or prostate cancer death). Among men with ERG-positive tumors, the multivariable hazard ratio for lethal prostate cancer was 1.48 (95% CI = 0.98 to 2.23) per 5-unit increase in BMI before diagnosis, 2.51 (95% CI = 1.26 to 4.99) per 8-inch increase in waist circumference before diagnosis, and 2.22 (95% CI = 1.35 to 3.63) per 5-unit increase in BMI at baseline. The corresponding hazard ratios among men with ERG-negative tumors were 1.10 (95% CI = 0.76 to1.59; P interaction = .24), 1.14 (95% CI = 0.62 to 2.10; P interaction = .09), and 0.78 (95% CI = 0.52 to 1.19; P interaction = .001). These results suggest that obesity is linked with poorer prostate cancer prognosis primarily in men with tumors harboring the gene fusion TMPRSS2:ERG.