Air pollution is a leading environmental cause of lung cancer, yet the underlying biological pathways remain poorly understood. Identifying circulating biomarkers that capture early molecular responses may clarify how air pollutants contribute to carcinogenesis and help identify individuals at elevated risk. We conduct a prospective nested case-control study within two Cancer Prevention Study cohorts, profiling more than 1100 metabolites in pre-diagnostic plasma samples from 1357 participants. Residential concentrations of six major air pollutants are estimated at the time of blood draw. Here we show that eight circulating metabolites are associated with both air pollution exposure and subsequent lung cancer risk. Four metabolites, including γ-glutamylglutamine, phenylacetylglutamate, N-(2-furoyl)glycine, and 4-vinylguaiacol glucuronide, significantly mediate associations for particulate matter and ozone (adjusted q-value < 0.2). These findings suggest that air pollution may promote lung cancer partly through metabolic pathways related to inflammatory and oxidative processes, providing key insights into potential mechanisms and targets for prevention. Exposure to ambient air pollution is an established risk factor for lung cancer. In here, the authors report multiple metabolic perturbations that may mediate the association between ambient air pollution exposure and lung cancer risk.
Sabrina S. Chow, Ying Wang, J. Sarnat et al.· Nature Communications· 0 citations
Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants associated with higher serum lipids, although primarily in cross-sectional studies, limiting causal inference. We aim to determine whether there is a causal relationship between PFAS and serum lipid levels by emulating a target trial of a hypothetical PFAS-reduction intervention using observational data. The target trial would enroll adults aged ≥20 years without prior cardiovascular, kidney, or liver disease, diabetes, or use of related medications. Participants would be randomly assigned to either PFAS-reduction counseling or no counseling, with adherence evaluated after 10 years, and then followed up after 10 years to assess effects on serum lipids. To emulate the target trial, we will use data from the Copenhagen City Heart Study on three successive clinical visits: baseline, follow-up, and outcome assessment visit, 10 years apart. Eligible participants meet the target trial criteria, have available blood samples for PFAS quantification at follow-up, and information on serum lipids at the outcome assessment. Intervention strategies will be evaluated based on observed reductions in PFAS concentrations between baseline and follow-up visit. Serum lipids are assessed at the outcome assessment visit. The emulation assumes exchangeability by adjusting for baseline and time-varying confounders using G-computation. This protocol explores applying the target trial emulation framework to improve causal inference in environmental epidemiology.
Georges Khoury, L. Deen, Lars Christian Lund et al.· Toxics· 0 citations
