Dietary influences on endocrine-inflammatory interactions in prostate cancer development

Prostate cancer is the most frequently diagnosed non-cutaneous cancer and is the second leading cause of cancer death in American men. The focus of this review is to define the relationship between hormonal (testosterone/estrogens) stimulation of chronic inflammation, generation of reactive oxygen species (ROS), and uncontrolled prostate cell proliferation, and review putative dietary chemoprevention strategies that focus on these processes. It has been proposed that elevated estrogen in men who already have high blood testosterone are at high risk for prostate cancer. We hypothesized that elevated estrogen, in the presence of testosterone, causes prolonged activation of a redox-sensitive transcription factor, nuclear factor kappa B (NFkappaB), that initiates and amplifies an inflammatory cascade within the prostate and results in sustained oxidative and nitrative damage. The inflammatory cascade is proposed to link with uncontrolled proliferation through up-regulated Wnt signal and abnormal catenin accumulation in the prostate. Finally, a strategy that emphasizes a "whole food" based approach to cancer prevention by selecting food products that bear anti-inflammatory and anti-proliferative properties may be most promising as an effective dietary chemopreventive strategy. (C) 2004 Elsevier Inc. All rights reserved.