Abstract
PURPOSE: Recent evidence suggests a significant association between microplastic (MPs), forever chemicals, and plasticizers and various diseases including cancer. Here, we evaluated the circulating levels of plastic-associated chemicals for lung cancer incidence and mortality among smokers in the Prostate Lung Colorectal and Ovarian (PLCO) study. EXPERIMENTAL DESIGN: Using mass spectrometry, we screened for 29 known MPs, forever plastics (per- and polyfluoroalkyl substances [PFAS]), and plasticizers chemicals in 245 sera collected preceding a lung cancer diagnosis and 1,200 non-case sera from participants in the PLCO study who had a history of smoking. Five PFAS and 3 plasticizers were detected and quantified in sera. A PFAP model, consisting of PFOS + PFHA + mono-iso-nonyl-phthalate, was developed for predicting lung cancer mortality and risk strata based on quantiles established. RESULTS: Higher circulating levels of PFOS, PFHA, and mono-iso-nonyl-phthalate were associated (p<0.05) with increased risk of lung cancer death but not incidence. Compared to the lowest quantile (reference), individuals with PFAP scores in the highest quantile were at markedly higher risk of death from lung cancer (p<0.0001), with respective cause-specific and sub-distributional HRs of 1.86 (95% CI: 1.18-2.93) and 1.82 (95% CI: 1.15 - 2.88). Sub-stratified analyses confirmed that the PFAP model remained an independent predictor of lung cancer-specific mortality (p < 0.05) across strata defined by age, sex, smoking history, histologic subtype, and stage at diagnosis. CONCLUSIONS: In the PLCO cohort elevated levels of PFOS, PFHA, and mono-iso-nonyl-phthalate were associated with increased lung cancer mortality among ever smokers across disease subgroups.