Prostate cancer risk and antioxidant biomarkers: the age-dependent reversal of bilirubin's role

Abstract

Background Prostate cancer incidence increases markedly after midlife, coinciding with age-related hormonal decline and alterations in antioxidant defense mechanisms. This study investigated age-specific associations between endogenous antioxidant markers (total bilirubin, albumin, and uric acid) and prostate cancer risk. Methods Data were derived from the Korean Cancer Prevention Study-II (KCPS-II), and a total of 83,371 men were included after excluding individuals with a history of cancer or missing key variables at baseline. Participants were categorized into four age groups: < 45, 45-55, > 55, and > 65 years. During a mean follow-up of 13.5 years, 705 incident cases of prostate cancer (ICD-10: C61) were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer per 1-standard deviation (SD) increase in each antioxidant marker were estimated using Cox proportional hazards models. Quartile and trend analyses were also performed. Results Total bilirubin showed a statistically significant negative association with prostate cancer risk in men aged 45-55 years (HR: 0.86, 95% CI: 0.75-0.98, p = 0.0208), while a significant positive association was observed in men over 65 years (HR: 1.21, 95% CI: 1.02-1.43, p = 0.0285). Albumin was not significantly associated with prostate cancer risk in most age groups, but a significant positive association was found in men under 45 years (HR: 1.41, 95% CI: 1.07-1.86, p = 0.0152). Uric acid showed a consistent positive association with prostate cancer risk in the overall population (HR: 1.13, 95% CI: 1.06-1.21, p = 0.0003), and in men aged < 45 years (HR: 1.15, 95% CI: 1.02-1.30, p = 0.0241), > 55 years (HR: 1.20, 95% CI: 1.08-1.32, p = 0.0005), and > 65 years (HR: 1.20, 95% CI: 1.04-1.38, p = 0.0121). Conclusions Total bilirubin was negatively associated with prostate cancer risk during the andropause period (ages 45-55), but this association reversed with increasing age. Uric acid consistently showed a positive association with prostate cancer risk across all age groups.