Long-term exposure to selected pollutants was associated with variations in PD-L1 expression and EGFR status, suggesting that environmental factors may contribute to tumor heterogeneity, but causal relationships cannot be established.
Abstract
Background/Objectives: Air pollution is progressively acknowledged not only as a carcinogenic exposure, but also as a potential modulator of tumor immune activation and molecular heterogeneity in lung cancer. However, integrated analyses combining long-term environmental exposure, molecular biomarkers and immune phenotype remain limited, especially in Eastern European populations. Methods: We conducted a regional retrospective study including patients diagnosed with lung cancer in Constanța County, Romania. Prolonged atmospheric pollution exposure over an average period of 15 years was estimated using historic environmental monitoring data. Tumor samples were assessed for histopathological subtype, PD-L1 expression and EGFR status, while ALK and KRAS alterations were descriptively analyzed because of the limited number of positive cases. Multivariate ordinal and binary logistic regression models and predicted probability analyses were used to evaluate the association between chronic pollution exposure, PD-L1 expression and EGFR positivity. Results: Chronic NO2 exposure was significantly associated with increased PD-L1 expression (OR = 1.035, p = 0.017), suggesting an association between NO2 exposure and an immune-related tumor phenotype. Similar trends were observed for PM10, NO and NOx exposures. Exploratory associations were observed between EGFR positivity and carbon monoxide exposure. Conclusions: Chronic atmospheric pollution was associated with differences in the immune and molecular profile of lung cancer. Long-term exposure to selected pollutants was associated with variations in PD-L1 expression and EGFR status, suggesting that environmental factors may contribute to tumor heterogeneity. However, causal relationships cannot be established from this retrospective observational study.
An increase in formaldehyde concentration in the air is associated with a gain in breast cancer incidence, especially at the early stages, and it is advisable to strengthen formaldehyde monitoring, implement molecular epidemiological screening of these polymorphisms and active detection of breast cancer in genetically determined risk groups.
O. N. Gulyaeva, Ivan E. Tereshkin, V. Kislitsyna et al.· Hygiene and Sanitation· 0 citations
Background: Environmental exposures are biologically plausible contributors to thyroid cancer outcomes, but population-based evidence is heterogeneous and often focuses on incidence rather than stage at diagnosis. Objective: This study aimed to evaluate whether ecological state-year environmental indicators add predictive information for advanced-stage thyroid cancer at diagnosis in a large SEER-based cohort (U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results Program). Methods: We conducted a retrospective registry-linked analysis of 368,726 SEER thyroid cancer cases with valid combined summary stage. Advanced stage was defined as regional or distant disease and occurred in 118,509 cases (32.14%). Environmental variables were linked as state-year indicators using five-year moving averages from the years preceding diagnosis. Regularized logistic regression, gradient boosting, and Extra Trees models evaluated incremental predictive performance. Results: Adding environmental variables to demographic, socioeconomic, histology, and laterality predictors produced small random-split improvements across model families. However, after SEER registry was added before environmental variables, the remaining environmental increment was minimal. Registry-group holdout validation did not support improved geographic generalizability from the environmental feature set. Conclusions: State-year environmental indicators carried limited predictive information for advanced thyroid cancer stage, and much of this information overlapped with registry and geographic structure. These findings clarify both the potential and limitations of ecological environmental linkage in SEER-based prediction studies.
Growing evidence links air pollution to colorectal cancer (CRC) incidence. We examined this association within the large Multiethnic Cohort Study (MEC). Geocoded residential addresses for 98,675 California MEC participants were appended to ambient air pollution measures of PM2.5 (particulate matter [PM] with an aerodynamic diameter <2.5μm), PM10 (PM <10μm), nitrogen dioxide (NO2), nitrogen oxides (NOx), carbon monoxide (CO), and ozone (O3), generated from enrollment (1993-1996) to December 31, 2018. Multivariable-adjusted Cox proportional hazards models evaluated associations of time-varying air pollutants with CRC incidence (n=3,217 cases). We assessed heterogeneity in associations by demographics, tumor stage, and anatomical subsite. CRC incidence increased with PM2.5 exposure (per 10μg/m3; hazard ratio [HR]=1.13, 95% confidence interval [CI]=0.96-1.33), mainly among female (HR=1.29, 95% CI=1.03-1.62) but not among male participants (Pheterogeneity=0.08). CRC incidence also increased with NOx exposure among female (HR=1.22, 95% CI=1.01-1.48) but not male participants (Pheterogeneity=0.07). Increased incidence associated with PM2.5 (HR=1.36, 95% CI=1.05-1.76), NO2 (per 20 parts per billion [ppb]; HR=1.32, 95% CI=1.05-1.68) and CO (per 1000 ppb; HR=1.36, 95% CI=1.01-1.84) exposures were observed for left colon and rectal cancers combined, but not right colon cancers (Pheterogeneity by site=0.08, 0.06 and 0.13, respectively). Associations of PM2.5 and NO2 with rectal cancer incidence differed by population group (Pheterogeneity=0.04 and 0.03, respectively), and was mostly driven by positive associations among Latino participants. In summary, increasing PM2.5, NO2, NOx, and CO exposures were suggestively associated with increased CRC incidence, particularly among female and Latino participants and for left colon and rectal cancers.
U. Ihenacho, Chiu‐Cheng Tseng, Jun Wu et al.· Environmental Research· 0 citations
BACKGROUND
Per- and polyfluoroalkyl substances are characterized by environmental persistence, bioaccumulation potential, and multi-organ toxicity. Given their ubiquitous presence in the environment and human serum, concerns regarding respiratory health risks are growing, particularly due to scarce evidence on environmental etiologies of chronic obstructive pulmonary disease in never-smokers. This study aimed to investigate the mechanistic role of these substances in chronic obstructive pulmonary disease through a population-computational-experimental paradigm, with specific focus on lipid-metabolic mediation.
METHODS
Data from the National Health and Nutrition Examination Survey (2007-2018) were analyzed using weighted quantile sum regression and quantile-based g-computation to assess mixture exposure effects. Mediation analysis was performed to evaluate the triglyceride-glucose index as a metabolic intermediate pathway. Network toxicology and molecular docking analyses were conducted to identify core protein targets. Human bronchial epithelial cells were exposed to perfluorooctanoic acid to validate target gene expression and downstream pathway activation.
RESULTS
Mixture exposure showed a significant positive association with chronic obstructive pulmonary disease risk. Perfluorooctanesulfonic acid and perfluorooctanoic acid were the primary toxicity contributors. The association remained robust among never-smokers. The triglyceride-glucose index significantly mediated the exposure-disease relationship (mediation proportion: 6.6%-7.8%). SRC, EGFR, PPARG, and MMP9 were identified as core targets. Experimental validation confirmed that perfluorooctanoic acid altered expression of these targets, activating inflammation and remodeling pathways.
CONCLUSIONS
These substances disrupt pulmonary homeostasis through concurrent molecular activation and lipid-metabolic disturbance, evidenced by triglyceride-glucose index mediation. This dual mechanism provides new evidence for chronic obstructive pulmonary disease prevention in never-smokers and identifies potential metabolic intervention targets.
Yansong Hu, Huanyu Cui, Yakun Wang et al.· BMC Pulmonary Medicine· 0 citations
BACKGROUND
Ambient air pollution may influence ovarian cancer risk but remains understudied. We examined long-term exposure to ambient nitrogen dioxide (NO2) in relation to the risk of invasive and borderline epithelial ovarian tumours.
METHODS
In a 2011-2016 population-based case-control study in Greater Montreal (Island of Montreal, North and South Shores), 473 cases and 887 controls provided residential postal codes at study participation, which were linked to mean NO2 concentrations from a national land-use regression (LUR) model. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for ovarian cancer overall. Polytomous logistic regression estimated associations for borderline and invasive tumours separately. Sensitivity analyses used NO2 concentrations from an alternative LUR model specific to the Island of Montreal.
RESULTS
For each interquartile range (IQR) increment (9.6 ppb) in ambient NO2, the OR (95% CI) of ovarian cancer overall was 1.07 (0.89-1.30), adjusted for age, education and area-level income. For borderline tumours, the adjusted OR (95% CIs) per IQR of NO2 was 1.36 (0.99-1.87), while for invasive cancer was 0.98 (0.79-1.21). Results were similar using NO2 estimates specific to the Island of Montreal, and with adjustment for fine particulate matter.
CONCLUSION
Our findings do not strongly support an association with invasive ovarian cancer, but suggest that air pollution, as indicated by NO₂ concentrations, may increase the risk of borderline tumours.
IMPACT
This study addresses an important gap, given limited previous work on air pollution and ovarian cancer, and brings new findings as the first to analyze borderline and invasive tumours separately.
Lysandre Viau, S. Buteau, Anita Koushik· Cancer Epidemiology, Biomark...· 0 citations
High-molecular-weight carcinogens significantly accumulate in human lungs in Northern Thailand, reflecting substantial environmental exposure, while tissue lipid content modulates toxin bioaccumulation, underscores an urgent need for targeted public health strategies addressing both environmental pollution and tobacco use.