Abstract B015: Potential systemic effects of beta-blocker use in prostate cancer patients

CANCER RESEARCH(2018)

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摘要
Background: In 2014, our group published an association between use of beta-blockers and superior prostate cancer (PCa) specific survival. Although debated, the association has also been observed in other cancer forms such as breast cancer and malignant melanoma. Although several potential mechanisms have been suggested, a biologic mechanism explaining these associations is still unknown. However, the diversity of cancer forms in which the association has been observed suggests that systemic mechanisms not directly related to prostate biology might play a role. Aim: In this project, we will look for potential biologic mechanisms explaining increased PCa specific survival time among beta-blocker users. Specifically, we will look for associations between known oncologic/immunologic markers and beta-blocker use prior to diagnosis. Method: We have selected 90 serum samples from PCa patients treated with radical prostatectomy at Oslo University Hospital, Aker, in the period 2006-2011. Clinical and pathologic information were coupled with data from the Norwegian Prescription Database, which records all use of prescription drugs by the Norwegian population. We calculated a propensity score, based on observed baseline characteristics including age, BMI and T-stage, using beta-blocker use as the outcome. We then selected the 45 beta-blocker users with most aggressive PCAs, and identified suitable controls using the propensity score. The serum samples were analyzed by OLINK Proteomics, using a semiquantitative reagent kit designed to measure 92 predefined and separate protein analytes related to immuno-oncology. Results and Conclusion: The statistical analysis is currently ongoing as of September 12th, 2017. Interesting finds, together with a brief overview of the method, will be presented at the conference. Based on previous findings on two different multiplex platforms, we have indications that serum levels of the proteins VEGF, IL6 and TNF might be different between beta-blocker users and non-users. Hence, we have a priori hypotheses regarding these proteins. After finishing the analysis of these proteins, we will run an open approach analysis to reveal if any other analytes differ with beta-blocker usage. We will also look for clustering of related proteins. The study design also allows for a more explorative analysis of associations between the analyzed proteins and prognostic factors, as well as follow-up (both biochemical recurrence free- and overall survival), not related to beta-blocker use. We consider this type of study to be a necessary step towards a potential future randomized clinical trial to assess beta blockers’ utility as adjuvant treatment for aggressive PCa. Citation Format: Helene H. Grytli, Haakon Ramberg, Peder R. Braadland, Heidi K. Nielsen, Ingrid J. Guldvik, Kristin A. Tasken. Potential systemic effects of beta-blocker use in prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B015.
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