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Lung Cancer Exposome in U.S. Military Veterans: Study of Environment and Epigenetic Factors on Risk and Survival
Background
The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.
Methods
This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.
Results
NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.
Conclusions
Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.
Background
The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.
Methods
This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.
Results
NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.
Conclusions
Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.
Background
The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.
Methods
This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.
Results
NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.
Conclusions
Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.