Dataset Information

Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG.

ABSTRACT:

Background

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.

Methods

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.

Results

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).

Conclusions

These results suggest that obesity is linked with poorer prostate cancer prognosis primarily in men with tumors harboring the gene fusion TMPRSS2:ERG.

SUBMITTER: Pettersson A

PROVIDER: S-EPMC3866157 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG.

Pettersson Andreas A Lis Rosina T RT Meisner Allison A Flavin Richard R Stack Edward C EC Fiorentino Michelangelo M Finn Stephen S Graff Rebecca E RE Penney Kathryn L KL Rider Jennifer R JR Nuttall Elizabeth J EJ Martin Neil E NE Sesso Howard D HD Pollak Michael M Stampfer Meir J MJ Kantoff Philip W PW Giovannucci Edward L EL Loda Massimo M Mucci Lorelei A LA

Journal of the National Cancer Institute 20131130 24

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 24292212

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Project description:Importance:Potential survival benefits from treating aggressive (Gleason score, ?7) early-stage prostate cancer are undermined by harms from unnecessary prostate biopsy and overdiagnosis of indolent disease. Objective:To evaluate the a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG (T2:ERG) RNA in the urine after digital rectal examination would improve specificity over measurement of prostate-specific antigen alone for detecting cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate the potential effect of such urine RNA testing on health care costs. Design, Setting, and Participants:Prospective, multicenter diagnostic evaluation and validation in academic and community-based ambulatory urology clinics. Participants were a referred sample of men presenting for first-time prostate biopsy without preexisting prostate cancer: 516 eligible participants from among 748 prospective cohort participants in the developmental cohort and 561 eligible participants from 928 in the validation cohort. Interventions/Exposures:Urinary PCA3 and T2:ERG RNA measurement before prostate biopsy. Main Outcomes and Measures:Presence of prostate cancer having Gleason score of 7 or higher on prostate biopsy. Pathology testing was blinded to urine assay results. In the developmental cohort, a multiplex decision algorithm was constructed using urine RNA assays to optimize specificity while maintaining 95% sensitivity for predicting aggressive prostate cancer at initial biopsy. Findings were validated in a separate multicenter cohort via prespecified analysis, blinded per prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) criteria. Cost effects of the urinary testing strategy were evaluated by modeling observed biopsy results and previously reported treatment outcomes. Results:Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85 years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved 95% sensitivity for detecting aggressive prostate cancer improved specificity from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years; range, 27-86 years), analysis confirmed improvement in specificity (from 17% to 33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P?=?.04), while high sensitivity (93%) was preserved for aggressive prostate cancer detection. Forty-two percent of unnecessary prostate biopsies would have been averted by using the urine assay results to select men for biopsy. Cost analysis suggested that this urinary testing algorithm to restrict prostate biopsy has greater potential cost-benefit in younger men. Conclusions and Relevance:Combined urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining robust sensitivity for detecting aggressive prostate cancer with consequent potential health care cost savings.

Dataset Information

Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG.

Background

Methods

Results

Conclusions

Publications

Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG.

Similar Datasets

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