Air Pollution, Lifestyle, and Genetic Risk: A Multidimensional Study of PM_2.5 Constituents and Prostate Cancer.

Abstract

To investigate the associations between long-term exposure to PM_2.5 chemical constituents and incident prostate cancer, considering potential effect modification by genetic susceptibility and lifestyle. We conducted a prospective study of 224,272 male participants from the UK Biobank with a median follow-up of 13.7 years. Individual exposures to PM_2.5 and its 5 key constituents (SO₄^2-, NO₃^-, NH₄⁺, elemental carbon, and organic matter) were modeled. Prostate cancer incidence was ascertained through national cancer registries. We used Cox proportional hazard models to estimate associations, quantile g-computation for joint effects, and interaction analyses to evaluate effect modification by lifestyle and polygenic risk scores (PRS). High exposures to PM_2.5, SO₄^2-, NO₃^-, and NH₄⁺ were significantly associated with increased prostate cancer risk, and NO₃^- showed the strongest association (HR per interquartile range: 1.088). The pollutant mixture had a positive joint effect, with NO₃^- contributing approximately 76.6% of this effect. Genetic predisposition, assessed by PRS, was a strong independent predictor of prostate cancer (HR for high vs low PRS: 6.527). No interaction effects were identified for the associations of lifestyle and PRS with PM_2.5 constituents. Specific PM_2.5 constituents, particularly NO₃^- and NH₄⁺, are associated with an elevated prostate cancer risk, independent of genetic and lifestyle factors. These findings suggest that public health interventions targeting air pollution sources and modifiable behaviors may help reduce disease burden.