User login
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.
MYO1E DNA Methylation in U.S. Military Veterans With Adenocarcinoma of the Lung Is Associated With Increased Mortality Risk
Project Purpose
The aim is to assess the role of MYO1E in survival among veterans with lung adenocarcinoma (LUAD).
Background
Veterans have a higher smoking exposure than civilians; a higher incidence of lung cancer; and a younger age at diagnosis of lung cancer. We recently showed that MYO1E DNA methylation and RNA expression in LUAD are associated with survival among civilians.
Methods
This is a retrospective cohort study involving LUAD among civilians and veterans with biopsy or pathologically proven LUAD from surgical specimens. DNA extraction and isolation from FFPE cancer tissues was performed using methylation-onbeads as previously published, followed by qMSP with bisulfite treatment to quantify DNA methylation. RNA extraction and quantification from lung tissues was obtained as described in previous publications.
Data Analysis
Differences were assessed with Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical. Two-tailed log-rank test was used to estimate overall survival differences and Cox hazard models, to quantify risk of mortality using hazard ratios (HRs) with 95% confidence intervals (CIs).
Results
There were 91 LUAD patients, 27 veterans and 64 civilians. Veterans were older than civilians, aged 70 years vs aged 66 years (P = .003); with higher proportions of males, 93% vs 69% (P = .03); higher proportion of African Americans, 67% vs 39% (P = .03); smoking more, 50 pack-year vs 40 (0.005), and having a higher proportion of grade I, 78% vs 55% (P = .036). Survival was statistically longer for MYO1E high DNA methylation group 48 months vs 33 for low methylation (P = .049). MYO1E RNA expression did not show statistically significant differences (P = .32). Multivariate Cox regression analysis adjusted by age, veteran/civil status, gender, race, packyear, and stage showed that DNA methylation was significantly associated with mortality risk (HR 5.14; 95% CI, 1.12-23.60) (P = .035).
Conclusions/Implications
This study suggests the utility of MYO1E DNA methylation as a prognostic biomarker for veterans with LUAD. Further studies are necessary to understand the role of MYO1E in chemotherapy resistance and microenvironment immune modulation. Given the low expression of MYO1E in blood cells, MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.
Project Purpose
The aim is to assess the role of MYO1E in survival among veterans with lung adenocarcinoma (LUAD).
Background
Veterans have a higher smoking exposure than civilians; a higher incidence of lung cancer; and a younger age at diagnosis of lung cancer. We recently showed that MYO1E DNA methylation and RNA expression in LUAD are associated with survival among civilians.
Methods
This is a retrospective cohort study involving LUAD among civilians and veterans with biopsy or pathologically proven LUAD from surgical specimens. DNA extraction and isolation from FFPE cancer tissues was performed using methylation-onbeads as previously published, followed by qMSP with bisulfite treatment to quantify DNA methylation. RNA extraction and quantification from lung tissues was obtained as described in previous publications.
Data Analysis
Differences were assessed with Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical. Two-tailed log-rank test was used to estimate overall survival differences and Cox hazard models, to quantify risk of mortality using hazard ratios (HRs) with 95% confidence intervals (CIs).
Results
There were 91 LUAD patients, 27 veterans and 64 civilians. Veterans were older than civilians, aged 70 years vs aged 66 years (P = .003); with higher proportions of males, 93% vs 69% (P = .03); higher proportion of African Americans, 67% vs 39% (P = .03); smoking more, 50 pack-year vs 40 (0.005), and having a higher proportion of grade I, 78% vs 55% (P = .036). Survival was statistically longer for MYO1E high DNA methylation group 48 months vs 33 for low methylation (P = .049). MYO1E RNA expression did not show statistically significant differences (P = .32). Multivariate Cox regression analysis adjusted by age, veteran/civil status, gender, race, packyear, and stage showed that DNA methylation was significantly associated with mortality risk (HR 5.14; 95% CI, 1.12-23.60) (P = .035).
Conclusions/Implications
This study suggests the utility of MYO1E DNA methylation as a prognostic biomarker for veterans with LUAD. Further studies are necessary to understand the role of MYO1E in chemotherapy resistance and microenvironment immune modulation. Given the low expression of MYO1E in blood cells, MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.
Project Purpose
The aim is to assess the role of MYO1E in survival among veterans with lung adenocarcinoma (LUAD).
Background
Veterans have a higher smoking exposure than civilians; a higher incidence of lung cancer; and a younger age at diagnosis of lung cancer. We recently showed that MYO1E DNA methylation and RNA expression in LUAD are associated with survival among civilians.
Methods
This is a retrospective cohort study involving LUAD among civilians and veterans with biopsy or pathologically proven LUAD from surgical specimens. DNA extraction and isolation from FFPE cancer tissues was performed using methylation-onbeads as previously published, followed by qMSP with bisulfite treatment to quantify DNA methylation. RNA extraction and quantification from lung tissues was obtained as described in previous publications.
Data Analysis
Differences were assessed with Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical. Two-tailed log-rank test was used to estimate overall survival differences and Cox hazard models, to quantify risk of mortality using hazard ratios (HRs) with 95% confidence intervals (CIs).
Results
There were 91 LUAD patients, 27 veterans and 64 civilians. Veterans were older than civilians, aged 70 years vs aged 66 years (P = .003); with higher proportions of males, 93% vs 69% (P = .03); higher proportion of African Americans, 67% vs 39% (P = .03); smoking more, 50 pack-year vs 40 (0.005), and having a higher proportion of grade I, 78% vs 55% (P = .036). Survival was statistically longer for MYO1E high DNA methylation group 48 months vs 33 for low methylation (P = .049). MYO1E RNA expression did not show statistically significant differences (P = .32). Multivariate Cox regression analysis adjusted by age, veteran/civil status, gender, race, packyear, and stage showed that DNA methylation was significantly associated with mortality risk (HR 5.14; 95% CI, 1.12-23.60) (P = .035).
Conclusions/Implications
This study suggests the utility of MYO1E DNA methylation as a prognostic biomarker for veterans with LUAD. Further studies are necessary to understand the role of MYO1E in chemotherapy resistance and microenvironment immune modulation. Given the low expression of MYO1E in blood cells, MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.