Outdoor Ultrafine Particulate Matter and Risk of Lung Cancer in Southern California

Rationale: Particulate matter <2.5 μm in aerodynamic diameter (PM_2.5) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter, 0.1 μm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged >50 years in southern California at enrollment (1995–1996) followed through 2017 for incident lung cancer (n = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM_2.5. In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm³ and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99–1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05–1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm³, 1.09 [95% CI, 1.00–1.18]), but no increased risk was apparent among women (P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02–1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with >10 years of residential duration (HR, 1.11 [95% CI, 0.98–1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung.