Association of Blood Levels of Forever Plastics with Lung Cancer Mortality among Ever Smokers in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cohort Study.

PURPOSE: Recent evidence suggests a significant association between microplastic (MP), forever chemicals, and plasticizers and various diseases, including cancer. In this study, we evaluated circulating levels of plastic-associated chemicals in relation to 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 MP, forever plastics [per- and polyfluoroalkyl substances (PFAS)], and plasticizer chemicals in 245 sera collected preceding a lung cancer diagnosis and 1,200 noncase sera from participants in the PLCO study who had a history of smoking. Five PFAS and three plasticizers were detected and quantified in sera. A PFAP model, consisting of perfluorooctane sulfonate (PFOS) + perfluorohexanesulfonic acid (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 with increased risk of lung cancer death (P < 0.05) but not incidence. Compared with 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 subdistributional HR of 1.86 [95% confidence interval (CI), 1.18-2.93] and 1.82 (95% CI, 1.15-2.88). Substratified 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.