Tracheal, bronchus, and lung (TBL) cancer stands as one of the significant contributors to cancer-related fatalities in U.S. as of 2023. It is projected to constitute 21% of cancer-related deaths and 12% of cancer diagnoses. Despite its profound impact on public health, TBL cancer exhibits a comparatively low survival rate (1, 2). According to the Cancer Tomorrow report by GLOBOCAN, incident cases of TBL in U.S. are forecasted to surge by approximately 38% by 2040, with mortality cases expected to rise by about 45%. Furthermore, the majority of TBL cancer cases in U.S. occur in individuals aged 50 and above. However, roughly 20% of total TBL cancer deaths are not linked to tobacco use, potentially placing it as the eighth most prevalent cause of cancer-related mortality (1, 3, 4).

According to the International Agency for Research on Cancer (IARC), outdoor air pollution is classified as a Group 1 human carcinogen and significantly contributes to the burden of diseases, including lung cancer (5). Moreover, ambient PM2.5 air pollution has been identified as a contributing factor in nearly 14.1% of lung cancer deaths globally (6). The persistence of unhealthy air pollution levels for more than one-third of Americans underscores the need for continued research and public health interventions (1, 4, 7). The evolutionary and developmental mechanisms underlying TBL cancer remain complex. Exposure to air pollution may play a role in the progression of TBL cancer through the activation of signal transduction pathways, DNA damage, inflammation, metabolism, and epigenetic regulation (8). Recent studies have revealed a mechanistic relationship between air pollution and lung cancer, both in functional mouse models and clinical cohorts (9–11).

Based on the findings from seven European cohorts participating in the “Effects of Low-level Air Pollution: a Study in Europe” (ELAPSE), researchers have discovered a significant link between long-term exposure to PM2.5 and an increased risk of lung cancer, even at concentrations below the current European Union (EU) limit values. Similarly, the Adventist Health and Smog Study-2 (AHSMOG-2) cohort study also observed significant positive associations between incident lung cancer and PM2.5 exposure, particularly among individuals who have never smoked or are past smokers, at low concentrations (12, 13). Moreover, a case study in Canada suggests that never-smoking patients have indicated relationships with air pollution exposures, and chronic exposure to home air pollution is linked to an elevated risk of lung cancer in Nepal among never-smokers (14, 15). Besides, more than half of lung cancer patients in Taiwan are individuals who have never smoked. Elevated levels of PM2.5 can influence both the occurrence and the survival of patients with adenocarcinoma lung cancer (16, 17). Similarly, in Pennsylvania and California, air pollution could affect the survival rates of lung cancer patients following diagnosis (18, 19).

Greenspace was considered to provide health benefits and higher access to greenspace is positively correlated with longer life expectancy (20–22). Exposure to green spaces is inversely associated with overall and cause-specific mortality, indicating that it provides a protective role (23–25). For TBL cancer, green spaces may act as a protective role or work as an effective tool to improve air quality. Studies in France and Belgium have reported varying associations between exposure to greenspace, cancer incidence, and mortality. However, a retrospective cohort study in Taiwan revealed that increased exposure to green space may mitigate the harmful impacts of PM2.5 and reduce the risk of lung cancer (26–28). For other cancers, including breast and prostate cancer, there might be a protective relationship between exposure to greenspace and the development of malignancies (29).

Despite extensive studies on the health benefits of green spaces and the detrimental effects of air pollution, the specific interactions between green space, air pollution, and TBL cancer at the state level in the United States remain underexplored. This study addresses the following gaps: (1) Limited exploration of green space and cancer links: While existing research validates the general health benefits of green spaces, there is a lack of detailed exploration regarding their specific association with TBL cancer. This study aims to provide a more comprehensive understanding of how green spaces influence TBL cancer incidence and mortality. (2) Reconfirmation of PM2.5 impact: Although the link between PM2.5 air pollution and TBL cancer has been established, this study reconfirms this connection within the context of green space exposure, emphasizing the need to consider multiple environmental factors simultaneously. (3) Need for nuanced analysis: Current research often overlooks the complex interactions between green spaces, air pollution, lung cancer, and varying population demographics. This study highlights the necessity of a more nuanced and precise analysis that accounts for these interactions to better inform future research and public health policies.

By addressing these gaps, the study aims to enhance our understanding of the interplay between environmental factors and TBL cancer, ultimately providing valuable insights for the development of more effective health interventions and policies. Therefore, in this study, we conducted a comprehensive analysis to assess the interplay between green spaces, air pollutant levels, and the risk of tracheal, bronchus, and lung (TBL) cancer across different age groups (over 20 years, 20–54 years, and over 55 years) at the state level in U.S. Furthermore, we explored potential underlying mechanisms by investigating their associations with meteorological, sociodemographic, and socioeconomic factors.

Although TBL cancer incidence and mortality in over 20 years subgroup peaked in 2019 with relatively similar numbers (86.87 in 2007; 82.33 in 2013, and 88.69 in 2019), overall trends remained consistent and declined over the three time periods. The overall incidence and mortality rates of adult TBL cancer for individuals aged 20–54 years and over 55 years decreased across the three time periods ( Table 1 ). The East South-Central region of U.S. showed higher rates of TBL cancer incidence and mortality among individuals over 55 years ( Figure 1 ). The overall mean NDVI values in U.S. ranged from 0.70 in 2007 to 0.71 in 2013 to 0.72 in 2019 ( Figure 1 ). The East and East Central regions of U.S. had higher mean NDVI values in 2007, 2013, and 2019. Conversely, the Western region, including states with high altitudes such as Arizona, Nevada, Utah, New Mexico, and Wyoming, exhibited comparatively lower NDVI values.

There was a strong correlation between PM2.5 and SO₂, while the other air pollutants showed weak to moderate relationships ( Supplementary Table S1 ). PM2.5, PM10, NO₂, and Ozone levels exhibited moderate and positive correlations with the annual average temperature. On the contrary, annual average precipitation was negatively and moderately correlated with PM10 and Ozone. Controlling for specific pollutants, NDVI was primarily associated with TBL cancer incidence and mortality in individuals over 20 years old across all three years ( Supplementary Table S2 ). We also employed a unified model to evaluate all three years, adjusting for meteorological and socio-demographic factors. In this analysis, the associations between NDVI, air pollutants, and TBL cancer incidence and mortality remained largely positive.

The study found a significant association between the NDVI and the incidence of TBL cancer in individuals aged 20 and above. Specifically, for PM2.5, the association was quantified with a β coefficient of 0.713 (95% CI: 0.856, 1.140; p < 0.01). Similar significant associations were observed for other air pollutants: PM10 (β = 0.756; 95% CI: 0.590, 0.922; p < 0.001), SO2 (β = 0.692; 95% CI: 0.525, 0.859; p < 0.001), NO2 (β = 0.730; 95% CI: 0.557, 0.903; p < 0.001), and Ozone (β = 0.808; 95% CI: 0.626, 0.990; p < 0.001).

Similarly, NDVI was associated with TBL cancer mortality in the same age group. The β coefficient for PM2.5 was 0.664 (95% CI: 0.426, 0.902; p < 0.01). For other pollutants, the associations were: PM10 (β = 0.748; 95% CI: 0.579, 0.917; p < 0.001), SO2 (β = 0.669; 95% CI: 0.496, 0.842; p < 0.001), NO2 (β = 0.712; 95% CI: 0.540, 0.884; p < 0.001), and Ozone (β = 0.796; 95% CI: 0.610, 0.982; p < 0.001) ( Table 2 ). Especially, more pronounced effects were observed among individuals aged 20 to 54 in terms of mortality (0.777 – 1.780) ( Table 2 ). These findings were further supported by subgroup analyses, which demonstrated statistically significant correlations in both middle-aged individuals (20–54 years old) and older adults (55 years and above), reinforcing the overall relationship between NDVI, air pollution, and TBL cancer outcomes. The consistent significance across multiple pollutants and age groups underscores the robustness of the observed associations and suggests a broad impact of vegetation and air quality on TBL cancer incidence and mortality.

Furthermore, the associations of PM2.5 with TBL cancer remained significantly positive after adjusting for meteorological and socio-demographic variables, ranging from 0.012 to 0.080. Notably, PM2.5 was associated with TBL cancer mortality in individuals aged 20–54 years (β = 0.076; 95% CI =0.070, 0.082; p < 0.001) for PM10, along with SO2, NO2, and Ozone (β = 0.062; 95% CI = 0.053, 0.070; p < 0.001), (β = 0.079; 95% CI = 0.072, 0.085; p < 0.001), and (β = 0.080; 95% CI = 0.073, 0.087; p < 0.001), respectively ( Table 3 ). Despite this, the associations for the other four pollutants were positive but not statistically significant ( Table 3 ).

Our interaction analysis between NDVI and ozone revealed positive associations with all TBL cancer rates, while concentrations of other air pollutants showed no significant associations. Interaction between PM2.5 and HDI showed a negative association (β = -0.324; 95% CI = -0.177, -0.471; p < 0.05) (β = -0.351; 95% CI = -0.484, -0.219; p < 0.01) with TBL cancer incidence and mortality in individuals over 20 years old. The interaction between PM2.5 and educational level was negatively associated with TBL cancer rates in all subgroups except for TBL cancer incidence in individuals aged over 55. Our interaction analysis between tobacco use and PM2.5 concentration levels indicated a positive association (β = 2.710; 95% CI = 1.510, 3.910; p < 0.05) (β = 2.710; 95% CI = 1.640, 3.780; p < 0.05) with TBL cancer incidence and mortality in individuals over 20 years old. Additionally, the interaction between max NDVI and HDI was negatively associated with TBL cancer incidence in the individuals aged 20–54 (β = -25.053; 95% CI = -13.052, -37.054; p < 0.05), as well as TBL cancer mortality in individuals aged 20 to 54 and those aged over 55 (β = -64.227; 95% CI = -18.502, -82.794; p < 0.001) (β = -25.053; 95% CI = -13.052, -37.054; p < 0.05) ( Table 4 ).

In the analysis of 18 states with increasing net forest coverage from 2000 to 2020, we observed additional effects between mean NDVI and health care coverage, health status, obesity rate, and participation in physical activities, separately. ( Supplementary Table S3 ). Regarding health care coverage, better health status, and participation in physical activities, NDVI indicated a protective role. However, when interacting with high BMI individuals, NDVI was positively associated with TBL cancer rates.

The graph depicts the TBL cancer incidence and mortality rates (per 100,000 population) among individuals aged over 55 years and the mean NDVI across 49 states in the United States for the years 2007, 2013, and 2019 ( Figure 2 ). The lines on the graph illustrate the temporal trends of the data series, with blue lines representing cancer incidence, orange lines representing cancer mortality, and green lines indicating the mean NDVI. The horizontal axis (X-axis) displays the three time periods (2007, 2013, and 2019), while the Y1-axis on the left side corresponds to the cancer rates, and the Y2-axis on the right side corresponds to the mean NDVI ( Figure 2 ). Selected states in U.S. of our study: (1) Alabama, (2) Arizona, (3) Arkansas, (4) California, (5) Colorado, (6) Connecticut, (7) Delaware, (8) District of Columbia, (9) Florida, (10) Georgia, (11) Idaho, (12) Illinois, (13) Indiana, (14) Iowa, (15) Kansas, (16) Kentucky, (17) Louisiana, (18) Maine, (19) Maryland, (20) Massachusetts, (21) Michigan, (22) Minnesota, (23) Mississippi, (24) Missouri, (25) Montana, (26) Nebraska, (27) Nevada, (28) New Hampshire,(29) New Jersey, (30) New Mexico, (31) New York, (32) North Carolina, (33) North Dakota, (34) Ohio, (35) Oklahoma, (36) Oregon, (37) Pennsylvania, (38) Rhode Island, (39) South Carolina, (40) South Dakota, (41) Tennessee, (42) Texas, (43) Utah, (44) Vermont, (45) Virginia, (46) Washington, (47) West Virginia, (48) Wisconsin, and (49) Wyoming ( Figure 2 ).

Figure 3 presents the mean NDVI and concentrations of PM2.5 and Ozone across states for the years 2007, 2013, and 2019. In the left panel, the association between the mean NDVI (Y-axis) and the levels of PM2.5 or Ozone concentration (X-axis) is depicted. The size and color of the bubbles indicate the TBL cancer incidence and mortality for each state across the three time periods. Note: The data are represented as asthma prevalence (cases per 100,000 population), NDVI as the mean value, PM2.5 (particulate matter of diameter 2.5 µm or smaller), PM10 (particulate matter of diameter 10 µm or smaller), NO₂ (nitrogen dioxide), SO₂ (sulfur dioxide), O₃ (ozone) in µg/m³, annual average temperature in degrees Fahrenheit, average annual precipitation in inches, GDP (gross domestic product), PD (population density) as persons/sqkm. Average values are presented as mean (± standard deviation), with minimum (Min) and maximum (Max) values, and percentile measures at 25th, 50th, 75th ( Figure 3 ).

In this research, we investigated the relationship between greenspace, air pollutant concentration, and TBL cancer across different age groups at the state level in U.S. Our findings uncovered a direct relationship between the average NDVI and PM2.5 levels with TBL cancer rates across all age groups, particularly notable in the 20 to 54 age range. This study stands as the first at the state level to identify such a connection. In our examination of interactions, we noted positive correlations between ozone and NDVI, as well as between PM2.5 and tobacco consumption. Conversely, we observed negative associations between PM2.5 concentration and educational attainment as well as HDI, and between maximum NDVI and HDI in the GEE models analyzing TBL cancer data.

Several studies have investigated the impact of greenspace on TBL cancer and other types of cancer. These studies have identified variability in the observed relationships, influenced by factors such as the type of greenspace, method of exposure measurement, individual attributes, and geographic location. For instance, studies in France and Spain found different results depending on the type of greenery. In France, spending more time near farmland was positively linked to a higher chance of getting breast cancer. Meanwhile, in Spain, it was linked to a higher risk of getting any type of cancer (26, 45). While exposure to neighborhood-level greenspace in Australia is speculated to be linked to higher risks of having skin cancer (46). In addition to a cross-sectional study conducted in Philadelphia, when green parcels as tiny as 1m² are included as greenspace, there is a positive correlation between the density of greenspace and both overall and cause-specific mortality (47). A recent meta-analysis compiled data from nine papers investigating the link between greenspace exposure and lung cancer, eventually, the combined findings suggested no significant association (29). Therefore, the relationship between green space and health appears to be nuanced, potentially varying based on geographical context, study methodologies, and the techniques used to assess exposure in the studies (48).

In U.S., the distribution of greenspace and air pollution concentrations varies from east to west, with both factors being linked to TBL cancer along with distinct socioeconomic variables and other correlated risk factors. This study represents the first attempt to investigate the relationship between greenspace, air pollutants, socioeconomic factors, and TBL cancer at the state level in U.S. By correlating and contrasting with existing research on air pollution, greenspace, and various diseases, this study contributes to a better understanding of the association between the natural environment and health issues.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.

JZ: Conceptualization, Writing – original draft, Writing – review & editing. RR: Conceptualization, Data curation, Methodology, Validation, Writing – original draft, Writing – review & editing. NB: Conceptualization, Data curation, Formal analysis, Writing – review & editing. MP: Conceptualization, Writing – review & editing. NX: Conceptualization, Writing – original draft, Writing – review & editing. PL: Conceptualization, Data curation, Writing – original draft, Writing – review & editing. WB: Conceptualization, Data curation, Writing – original draft, Writing – review & editing. ZM: Conceptualization, Data curation, Writing – review & editing, Writing – original draft. HP: Conceptualization, Data curation, Writing – original draft, Writing – review & editing. KV: Formal analysis, Writing – review & editing. VN: Writing – review & editing. RF: Conceptualization, Writing – review & editing. JL: Writing – original draft, Writing – review & editing.