Ambient air pollution exposure and lung cancer risk in a large prospective U.S. cohort

Outdoor air pollution, including fine particulate matter (PM_2.5), is an established cause of lung cancer; however, few studies have evaluated associations by histologic subtype.

We estimated outdoor PM_2.5 and nitrogen dioxide (NO₂) concentrations at the residential enrollment (1995-1996) address for 486,101 participants of the NIH-AARP Diet and Health Study, a cohort located in 6 states and 2 metropolitan areas. We used annual estimates from a national spatiotemporal model to assess concentrations for a 5-year pre-enrollment period (1990-1994). We used Cox regression to estimate hazard ratios and 95 % confidence intervals (HR [CI]) for associations with incident lung cancer overall and by histologic subtype per IQR increase in PM_2.5 and NO₂. Models were adjusted for demographic characteristics, smoking status and intensity, and census tract-level median household income; we separately evaluated the joint effects for both pollutants. We evaluated effect modification by smoking status, sex, and study catchment area, and evaluated statistical interaction via Wald tests.

22,453 lung cancers were diagnosed in follow-up through 2018. For PM_2.5, we observed a small increased risk of lung cancer overall (HR = 1.01[0.99-1.03] per 4.4 μg/m³). Associations were stronger for adenocarcinoma (HR = 1.05[1.01-1.09]) and squamous cell carcinoma (HR = 1.05[1.00-1.10]). In models of NO₂, a 10.4 ppb increase was associated with lung cancer overall (HR = 1.02[1.00-1.04]) and adenocarcinoma (HR = 1.06[1.03-1.09]). When both pollutants were considered simultaneously, stronger associations were noted between squamous cell carcinoma and PM_2.5 and between adenocarcinoma and NO₂. No clear differences in risk were noted by smoking status or sex (p-interaction all >0.05). Associations varied widely between the 8 cohort catchment areas (p-interaction <0.01).

Our findings from this large U.S. cohort indicate that risk of squamous cell carcinoma increases with PM_2.5 and adenocarcinoma with NO₂. Observed heterogeneity in associations by region suggesting that PM_2.5 constituency may influence differences in lung cancer risk.