Prospective Metabolomic Cohort of 123,037 Men Reveals Lipid Mediators Linking Air Pollution to Benign Prostatic...

Benign prostatic hyperplasia (BPH) is increasingly prevalent among aging male populations and is often accompanied by a lower urinary tract symptoms (LUTS). This study aimed to comprehensively analyze the impact of air pollution and lifestyle on the incidence of BPH and LUTS. In a prospective study-based U.K. Biobank (UKB) cohort, every 1 μg/m³ increase of PM_2.5 was associated with a 2.18% increased risk of BPH (P = 0.0029). Furthermore, PM_2.5-10, PM₁₀, NO₂, and NO _X also showed similar risk effects. As for mixed exposures, the weighted quantile sum (WQS) and quantile g-computation (qgcomp) method indicated that for each additional unit, the risk of BPH increased by 3.53% (P = 0.0265) and 2.20% (P < 0.0001). Analyses of LUTS in males showed that for each additional unit of mixed exposure, the risk of LUTS increased by 6.78% (P < 0.0001) and 9.17% (P < 0.0001). A cross-country cohort in western China was also replicated. As for single air pollutant exposure, the risk of BPH increased by 2.77% (P < 0.0001) for every 1 μg/m³ increase of PM_2.5. The other single and mixed pollutants also remained dangerous. Further analysis revealed that each additional 1 μg/m³ of PM_2.5 increased 2.34% risk of LUTS (P = 0.0014). The other pollutants also remained dangerous. The same applies to other single and mixed pollutants. The restricted cubic spline (RCS) curve found that there was a dose-response relationship between PM_2.5 concentration and BPH risk (P = 0.0169) and determined that 9.83 μg/m³ was the risk threshold for BPH. Compared with participants' exposure to low PM_2.5 and low-fat diet, participants with high PM_2.5 exposure and high-fat diet had 16% increased risk of BPH (P < 0.0001). Mediation analysis identified 34 lipid-related metabolites as potential mediators. This study emphasizes the significance of environmental and lifestyle factors in the prevention and management of BPH.