Outdoor air pollution and prostate cancer risk in the National Institutes of Health–AARP Diet and Health Study

Abstract Background Outdoor air pollution, including fine particulate matter (PM2.5), is an established carcinogen, yet few studies evaluate its associations with prostate cancer risk, and findings are mixed. Methods We used spatiotemporal prediction models to estimate annual average historical residential PM2.5 (1980-2017) and nitrogen dioxide (NO2) (1990-2017) concentrations for 289 299 men aged 50 years and older in the National Institutes of Health–AARP Diet and Health Study, enrolled from 6 states and 2 metro areas in 1995-1996, followed through 2018. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals of associations between 5-year average PM2.5 and NO2 and incident prostate cancer, overall and by tumor aggressiveness (ie, advanced [n = 5791], high-grade [ie, Gleason score ≥8, n = 5793], fatal [n = 3057]). We evaluated interactions with hypothesized effect modifiers. Results Historical PM2.5 and NO2 concentrations were not associated with prostate cancer risk overall (10-year lagged PM2.5 HR per 5 µg/m3 = 1.00, 95% confidence interval [CI] = 0.98 to 1.02; 10-year lagged NO2 HR per 10 ppb = 1.00, 95% CI = 0.98 to 1.01). Some positive trends were observed for aggressive disease (eg, high-grade: 10-year lagged PM2.5 HR = 1.03, 95% CI = 0.99 to 1.09; advanced: 10-year lagged NO2 HR = 1.04, 95% CI = 0.99 to 1.08). Stratified analyses also showed stronger associations for aggressive disease among Hispanic men (eg, high-grade: NO2 HR = 1.25, 95% CI = 1.05 to 1.48; P = .01 for interaction). Heterogeneity was also evident by urbanicity (high-grade: P = .01 for interaction, PM2.5 and NO2) and state (advanced: P = .05 for interaction, NO2), potentially reflecting air pollution mixture heterogeneity. Conclusions In this large US cohort, historical residential PM2.5 or NO2 concentrations were not associated with prostate cancer risk overall; however, risk was elevated in some subgroups and for aggressive outcomes. Future evaluation of air pollution mixture components may clarify observed subgroup differences.