Abstract 3618: Peripheral cytokine profiles and prostate cancer risk in CLUE II.
Authors: Bhavsar Nrupen A. , Bream Jay J. , Meeker Alan K. , Drake Charles G. , Peskoe Sarah B. , De Marzo Angelo M. , Isaacs William B. , Platz Elizabeth A. 
Published: August 2014

Abstract
Background
Recent evidence suggests a role for inflammation in the etiology of prostate cancer. Cytokines are important regulators of immune response, including in cancer. In the context of cancer, Th1 cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and, to some extent, interleukin (IL)-6, can elicit immune reactions to tumor cells. IL-1β, IL-8, IL-10, and IL-12p70 may suppress immune response to a tumor. Immune profile may be an important prognostic factor for disease-free survival in cancer patients. Whether the circulating cytokine profile influences prostate cancer incidence is understudied. Thus, we evaluated the cytokine-prostate cancer association prospectively.
Methods
We conducted an age-race matched case-control study (268 pairs) of inflammatory cytokines (IFN-γ, IL-10, IL-12-p70, IL-1β, IL-6, IL-8, and TNF-α), measured using the ultrasensitive Meso Scale Discovery (MSD) platform, and incident prostate cancer in CLUE II. Cases were identified by cancer registry linkage. The odds ratio (OR) and 95% confidence interval (95% CI) of prostate cancer by quartile of cytokine was calculated using matched and multivariable-adjusted conditional logistic regression.
Results
Median concentrations of IFN-γ (p=0.002), TNF-α (p=0.04), and IL-6 (p=0.06) were lower in cases than controls. Concentrations of the other cytokines did not differ by case status. The multivariable-adjusted OR of prostate cancer decreased across quartiles of IFN-γ (p-trend=0.004), TNF-α (p-trend=0.03), and IL-6 (p-trend=0.005). After their mutual adjustment, the patterns of association remained the same. Of note, the highest (vs lowest) quartile of TNF-α (p=0.03) and IL-6 (p=0.001) was associated with lower risk of metastatic prostate cancer with high Gleason sum ≥7. Overall prostate cancer risk did not change across quartiles of the other cytokines, including IL-10, a Th2 cytokine. However, in normal weight men, higher IL-10 concentration was inversely associated with prostate cancer (highest vs lowest quartiles: OR=0.36; 95% CI: 0.19-0.68), whereas in overweight and obese men, IL-10 was not inversely associated with risk (OR=1.32; 95% CI: 0.87-1.97; p-interaction=0.001). Significant interactions with BMI were not observed for the other cytokines.
Conclusion
Men with a prediagnostic circulating cytokine profile indicative of Th1 immune response may have a lower risk of prostate cancer, including aggressive disease. Whether this circulating cytokine profile reflects 1) the intraprostatic immune environment in benign tissue that protects against the development of prostate cancer, 2) the immune milieu in response to a yet undetected prostate adenocarcinoma that inhibits its growth and thus detectability, and/or 3) a systemic immune profile that mediates the influence of modifiable factors on prostate cancer risk, warrants additional study. The IL-10-obesity interaction also warrants further study.
Citation Format: Nrupen A. Bhavsar, Jay J. Bream, Alan K. Meeker, Charles G. Drake, Sarah B. Peskoe, Angelo M. De Marzo, William B. Isaacs, Elizabeth A. Platz. Peripheral cytokine profiles and prostate cancer risk in CLUE II. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3618. doi:10.1158/1538-7445.AM2013-3618