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Background <p>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.</p> Methods <p>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: &lt; 45, 45–55, &gt; 55, and &gt; 65&#xa0;years. During a mean follow-up of 13.5&#xa0;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.</p> Results <p>Total bilirubin showed a statistically significant negative association with prostate cancer risk in men aged 45–55&#xa0;years (HR: 0.86, 95% CI: 0.75–0.98, <i>p</i> = 0.0208), while a significant positive association was observed in men over 65&#xa0;years (HR: 1.21, 95% CI: 1.02–1.43, <i>p</i> = 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&#xa0;years (HR: 1.41, 95% CI: 1.07–1.86, <i>p</i> = 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, <i>p</i> = 0.0003), and in men aged &lt; 45&#xa0;years (HR: 1.15, 95% CI: 1.02–1.30, <i>p</i> = 0.0241), &gt; 55&#xa0;years (HR: 1.20, 95% CI: 1.08–1.32, <i>p</i> = 0.0005), and &gt; 65&#xa0;years (HR: 1.20, 95% CI: 1.04–1.38, <i>p</i> = 0.0121).</p> Conclusions <p>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.</p>

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

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  • 发表日期：

    2025年12月24日

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  • Jong Won Shin,
  • Jae Woong Sull,
  • Nguyen Thien Minh,
  • Sun Ha Jee

摘要

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.