Background Prostate specific antigen (PSA) and PSA velocity (PSAV, rate of PSA change over time) are biomarkers for diagnosis and prognosis of prostate cancer (PCa). Men who are at high risk for PCa also have associated co-morbidities for which they are taking NSAIDs and statins for long periods; therefore it is important to understand the effect of these medications on markers used to assess PCa risk. Methods Using a population of 699 men, multiple linear regressions were used to investigate the associations between PSA and concomitant medications; and mixed effects models were used to investigate these associations with PSAV. Results After adjusting for selenium use, age, race, body mass index, and pack-years of smoking; aspirin, other NSAIDs, or statins did not demonstrate statistically significant associations with PSA (p = 0.79, 0.68, and 0.79 respectively) or PSAV (p = 0.23, 0.43, and 0.84 respectively). Results were not altered upon stratifying the sample between men who developed PCa during the course of the study and those who did not. Conclusions Results from this study indicate that chronic use of aspirin, other NSAIDs, or statins did not impact PSA levels or PSAV in men at high risk for PCa. Larger prospective studies designed to investigate these relationships are needed to confirm this result. Impact Long-term use of NSAIDs or statins in men at high risk for PCa may not interfere with the diagnosis or prognosis of this disease, and supports appropriate use of these medications with regard to PCa risk.

Objectives: To determine the effect of selenium supplementation on the human proteomic profile. Design: Serum samples were collected in this pilot study from a randomized placebo controlled Phase 2 Watchful Waiting (WW) clinical trial. Setting: Subjects were followed every three months for up to five years at the University of Arizona Prostate Cancer Prevention Program Clinic. Participants: One hundred and forty men (age < 85 years) had biopsy-proven prostate cancer, a Gleason sum score less than eight, no metastatic cancer, and no prior treatment for prostate cancer. Intervention: As part of the WW trial, men were randomized to placebo, selenium 200 μg/day or selenium 800 μg/day. For the purpose of the current study, 40 subjects enrolled in the WW study (20 from the placebo group and 20 from Se 800 μg/day group) were selected. Measurements: Baseline serum samples were collected at each follow-up visit and stored at -80 degrees Celsius. A multiplexed proteomic panel investigated changes in 120 proteins markers simultaneously. Results: Thirteen proteins (Apolipoprotein J, IL-10, IL-1 alpha, MMP-3, IL-12p70, IL-2 receptor alpha, cathepsin B, eotaxin, EGFR, FGF-basic, myeloperoxidase, RANTES, TGF-beta) were determined to be either statistically (p-value < 0.05) or marginally significantly (0.05 < p-value <0.1) changed in the selenium supplemented group as compared to placebo. Conclusion: Although independent validation of these results is needed, this study is the first of its kind to utilize high throughput fluorescence based protein multiplex panel in analyzing changes in the proteomic profile due to selenium supplementation. Results from this study provide insight into the ability of selenium to modulate numerous protein markers and thus impact various biological processes in humans.

92 Background: Although ERG and PTEN expression has demonstrated to have a role in prostate carcinogenesis, its association with important clinical markers such as PSA velocity (rate of prostate specific antigen [PSA] change over time) is currently unknown. This novel pilot study presents the results of the above association with the aim of understanding its clinical utility. Methods: Data for this study was obtained from men enrolled in a phase 2 clinical trial conducted to determine the effect of selenium supplementation on prostate cancer progression. All men in this trial were diagnosed with prostate cancer and opted for watchful waiting as their treatment modality. Biopsy tissue collected at randomization was stained for ERG and PTEN using immunohistochemistry techniques. PSA was measured at baseline and at each follow-up visit (every three months). PSA velocity was calculated using mixed effects regression models and the study group was divided into three tertiles. Results: Data from 77 subjects indicates ERG and PTEN expression is independently associated with lower PSA velocity (p = 0.02 and 0.037 respectively). Joint effect of ERG and PTEN expression on PSA velocity was also analyzed using logistic regression. As compared to the wild type (ERG+/PTEN-), ERG-/PTEN- and ERG-/PTEN+ subjects demonstrated increased risk for high PSA velocity. Odds ratios (95% confidence intervals) are: 4.05 (0.68, 24.1) and 1.71 (0.12, 23.1), respectively. These models were adjusted for age, race and Gleason score. Conclusions: This is the first study to report on an association between ERG-PTEN expression and PSA velocity, an important clinical marker of aggressive prostate cancer. Results of this study are counterintuitive to the current understanding of ERG-PTEN mechanism in prostate carcinogenesis indicating presence of yet undiscovered molecular pathways. Hence further research is needed to delineate these pathways and determine clinical utility of ERG and PTEN expression in prostate cancer.

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