Advanced but Not Localized Prostate Cancer is Associated With Increased Oxidative Stress

Abstract

Oxidative damage has been linked to prostate carcinogenesis but its role in disease development and progression remains elusive. We investigated associations between indexes of oxidative stress with localized and advanced prostate cancer. Specifically we assessed the susceptibility of serum lipids to copper induced peroxidation (oxidizability). Serum oxidizability, and levels of alpha-tocopherol, malonyldialdehyde and uric acid were assessed in samples from 79 patients with prostate cancer, including 42 with localized and 37 with metastatic disease receiving androgen deprivation therapy, and 25 control subjects. Oxidizability was assayed by continuous spectroscopic monitoring of the accumulation of peroxidation products. The lag preceding oxidation, that is the delay between the induction and propagation of the reaction, served as a measure of the resistance of serum lipids to oxidation. Compared to control subjects patients with localized prostate cancer had no difference in oxidative stress indexes, whereas those with metastatic disease had a shorter lag preceding oxidation and increased malonyldialdehyde (p <0.05), each reflecting a state of high oxidative stress. In patients with prostate cancer the probability of disease progression from localized to advanced state increased with a shorter lag preceding oxidation (p <0.001), increased malonyldialdehyde (p <0.03) and decreased uric acid (p <0.04). Localized and metastatic disease was associated with increased rather than decreased alpha-tocopherol (p <0.008 and <0.005, respectively). Patients with advanced prostate cancer are subject to high oxidative stress, as determined by increased susceptibility of serum lipids to peroxidation. This association was not detected in patients with localized cancer and it is not attributable to altered levels of alpha-tocopherol.