Abstract A18: Pre-diagnostic serum antioxidant levels and prediction of TMPRSS2:ERG fusion status in prostate cancer

Abstract

Abstract Background: The TMPRSS2:ERG gene fusion is a distinct molecular subtype of prostate cancer characterized by chromosomal rearrangements joining the androgen responsive TMPRSS gene with ERG, an oncogenic member of the ETS gene family. TMPRSS2:ERG is thought to be an early pathologic event occurring in 50% of prostate tumors and resulting in more than 100,000 fusion positive cancer cases each year in the US. No studies to date have examined underlying risk factors associated with development of the fusion. Oxidative stress and the production of free radicals may result in chromosomal instability and predispose to the formation of TMPRSS2:ERG positive prostate cancer. Higher levels of serum antioxidants prior to prostate cancer diagnosis may therefore be protective against later development of fusion positive cancer. Methods: We undertook a case-control analysis nested within the prospective Physicians' Health Study and the Health Professionals Follow-up Study among men with prostate cancer (n=331) and age-matched controls (n=2139). The cohorts include pre-diagnostic bloods with antioxidant levels at baseline as well as tumor tissue to characterize TMPRSS2:ERG status among prostate cancer cases. We used multivariate logistic regression analysis to determine if plasma antioxidant levels influenced the development of the TMPRSS2:ERG fusion. Results: Of seven antioxidants examined (alpha-tocopherol, alpha-carotene, beta-carotene, beta-cryptoxanthin, gamma-tocopherol, lutein, and lycopene), levels of beta-carotene above the lowest quartile were protective against fusion positive vs. fusion negative prostate cancer (OR 0.49, 95% CL 0.28-0.86, p = 0.01). This association was driven by a non-significantly decreased risk of fusion positive cancer vs. controls (OR 0.75, 95% CL 0.51-1.09, p = 0.13) and a significantly increased risk of fusion negative cancer vs. controls (OR 1.58, 95% CL 1.03-2.41, p = 0.03). None of the six other antioxidants were associated with fusion status, and none of the antioxidants, including beta-carotene, predicted overall prostate cancer risk. Discussion: Previous studies examining antioxidant status and overall prostate cancer risk have been inconclusive. This is the first study to examine pre-diagnostic serum antioxidant levels in relationship to fusion status. We find that beta-carotene levels may alter prostate cancer risk based on molecular subtype. Citation Format: Gregory Judson, Andreas Pettersson, Allison Meisner, Lorelei Mucci. Prediagnostic serum antioxidant levels and prediction of TMPRSS2:ERG fusion status in prostate cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A18.