Analysis of the Potential Mediating Role of Plasma Proteins in the Association Between Air Pollution Exposure and Lung Cancer Risk Among Ever-Smokers
7 affiliations
- 1Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States 30322
- 2Department of Population Science, American Cancer Society, Atlanta, Georgia, United States 30303
- 3Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain 08003
- 4Universitat Pompeu Fabra (UPF), Barcelona, Spain 08003
- 5Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia 30322, United States
- 6CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain 28029
- 7Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France 69366
Abstract
The biological mechanisms linking air pollution to lung carcinogenesis remain underexplored. This study aimed to identify key proteins and pathways involved in mediating the effects of air pollutants on lung cancer risk. We analyzed 95 matched lung cancer case–control pairs of ever-smokers with prediagnosis plasma protein profiles measured in the Cancer Prevention Study-II Nutrition Cohort. We assessed associations between protein levels and six individual air pollutants, air pollution mixture, and lung cancer risk, adjusting for confounders and multiple testing. We identified overlapping proteins and enriched pathways associated with both exposures and lung cancer risk, followed by an exploratory high-dimensional mediation analysis (HIMA) to investigate the potential mediating roles of proteins. Seventeen proteins were associated with both exposures and lung cancer, including CX3CL1, ADAM15, and CXCL17 (P < 0.05). HIMA identified six proteins, including CX3CL1 and CXCL17, as potential mediating proteins of individual pollutant-lung cancer associations (Bonferroni-corrected P < 0.05), while these findings did not remain significant when excluding cases diagnosed within one year of blood draw. The exploratory results suggest that proteins and pathways related to inflammatory chemokine signaling, immune modulation, and altered cell proliferation, migration, and survival may play significant roles in air pollution-lung cancer association among ever-smokers.
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BibTeX
@article{tang2026analysis,
title = {{Analysis of the Potential Mediating Role of Plasma Proteins in the Association Between Air Pollution Exposure and Lung Cancer Risk Among Ever-Smokers}},
author = {Ziyin Tang and Donghai Liang and Jeremy A. Sarnat and W. Ryan Diver and Todd M. Everson and Emily Deubler and Youran Tan and Aparna H. Kesarwala and Michelle C. Turner and Mattias Johansson and Hilary A. Robbins and Carmen J. Marsit and Alpa V. Patel and Ying Wang},
journal = {Environmental Science \& Technology},
year = {2026},
month = oct,
doi = {10.1021/acs.est.6c07407},
url = {https://doi.org/10.1021/acs.est.6c07407},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Analysis of the Potential Mediating Role of Plasma Proteins in the Association Between Air Pollution Exposure and Lung Cancer Risk Among Ever-Smokers
AU - Ziyin Tang
AU - Donghai Liang
AU - Jeremy A. Sarnat
AU - W. Ryan Diver
AU - Todd M. Everson
AU - Emily Deubler
AU - Youran Tan
AU - Aparna H. Kesarwala
AU - Michelle C. Turner
AU - Mattias Johansson
AU - Hilary A. Robbins
AU - Carmen J. Marsit
AU - Alpa V. Patel
AU - Ying Wang
PY - 2026
DA - 2026/10/19
JO - Environmental Science & Technology
DO - 10.1021/acs.est.6c07407
UR - https://doi.org/10.1021/acs.est.6c07407
AB - The biological mechanisms linking air pollution to lung carcinogenesis remain underexplored. This study aimed to identify key proteins and pathways involved in mediating the effects of air pollutants on lung cancer risk. We analyzed 95 matched lung cancer case–control pairs of ever-smokers with prediagnosis plasma protein profiles measured in the Cancer Prevention Study-II Nutrition Cohort. We assessed associations between protein levels and six individual air pollutants, air pollution mixture, and lung cancer risk, adjusting for confounders and multiple testing. We identified overlapping proteins and enriched pathways associated with both exposures and lung cancer risk, followed by an exploratory high-dimensional mediation analysis (HIMA) to investigate the potential mediating roles of proteins. Seventeen proteins were associated with both exposures and lung cancer, including CX3CL1, ADAM15, and CXCL17 (P < 0.05). HIMA identified six proteins, including CX3CL1 and CXCL17, as potential mediating proteins of individual pollutant-lung cancer associations (Bonferroni-corrected P < 0.05), while these findings did not remain significant when excluding cases diagnosed within one year of blood draw. The exploratory results suggest that proteins and pathways related to inflammatory chemokine signaling, immune modulation, and altered cell proliferation, migration, and survival may play significant roles in air pollution-lung cancer association among ever-smokers.
SN - 0013-936X
SN - 1520-5851
ER -