Title | Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Pettersson A, Lis RT, Meisner A, Flavin R, Stack EC, Fiorentino M, Finn S, Graff RE, Penney KL, Rider JR, Nuttall EJ, Martin NE, Sesso HD, Pollak M, Stampfer MJ, Kantoff PW, Giovannucci EL, Loda M, Mucci LA |
Journal | J Natl Cancer Inst |
Volume | 105 |
Issue | 24 |
Pagination | 1881-90 |
Date Published | 2013 Dec 18 |
ISSN | 1460-2105 |
Keywords | Aged, Aged, 80 and over, Biomarkers, Tumor, Body Mass Index, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Male, Middle Aged, Obesity, Odds Ratio, Oncogene Proteins, Fusion, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prostatectomy, Prostatic Neoplasms, Surveys and Questionnaires, Up-Regulation, Waist Circumference |
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. |
DOI | 10.1093/jnci/djt332 |
Alternate Journal | J Natl Cancer Inst |
PubMed ID | 24292212 |
Grant List | CA-40360 / CA / NCI NIH HHS / United States CA-34944 / CA / NCI NIH HHS / United States HL-34595 / HL / NHLBI NIH HHS / United States HL-26490 / HL / NHLBI NIH HHS / United States R25 CA098566 / CA / NCI NIH HHS / United States CA141298 / CA / NCI NIH HHS / United States CA55075 / CA / NCI NIH HHS / United States U01 CA113913 / CA / NCI NIH HHS / United States 5P50CA090381-08 / CA / NCI NIH HHS / United States CA-097193 / CA / NCI NIH HHS / United States P01 CA055075 / CA / NCI NIH HHS / United States CA13389 / CA / NCI NIH HHS / United States T32 CA009001 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.