| Summary: | Background: Recent studies suggest that high pre-diagnostic serum concentrations of persistent organic pollutants (POPs) might result in the development of cancers in the general population. However, the association between pre-diagnostic serum POP concentrations and lung cancer risk has not been studied. Here, we evaluated associations between low-dose environmental exposure to POPs and risk of lung cancer using pre-diagnostic serum samples in a case-cohort study based on a population-based prospective cohort. Methods: We conducted a case-cohort study based on the Korean National Cancer Center Community Cohort, from which we included 118 lung cancer cases and 252 controls. Serum concentrations of POPs were measured by high resolution gas chromatography/high-resolution mass spectrometry, and data were analyzed using multivariable Cox proportional-hazards regression models. Results: Risk of lung cancer increased per unit increase in the natural log-transformed concentrations of the sum of chlordane congeners, total PCBs, and all PCBs subgrouped by the number of chlorines or ortho- substituted chlorines on the molecules, except for tri/tetrachlorobiphenyls, in all models. Among individual POP analytes with a detection rate >80%, after Bonferroni adjustment, only trans-nonachlor was associated with lung cancer risk. In categorical models, risk of lung cancer was associated with serum concentration of chlordane (4th vs. 1st quartile, hazard ratio [95% confidence interval], 8.79 [2.77–27.97]). Dose-dependent relationships were also found between risk of lung cancer and serum concentrations of PCBs regardless of their degree of chlorination, substitution pattern, or binding affinity to receptors (total PCBs, P = 0.002; mid-chlorinated PCBs, P = 0.004; high-chlorinated PCBs, P < 0.001; non- and mono-ortho PCBs, P = 0.031; di-ortho PCBs, P = 0.003; PCBs with dioxin-like activity, P = 0.011; non-dioxin-like non-/mono-ortho PCBs, P = 0.060). Conclusions: Serum concentrations of chlordane and PCBs are associated with risk of lung cancer in the general population, even decades after the ban on their production and use.
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