Linking Air Pollution and Hematologic Malignancies: From Epidemiology to Molecular Mechanisms.

Introduction

Hematologic malignancies represent a growing global health burden, with incidence steadily increasing in recent decades and projected to continue rising [ 1 , 2 ]. This trend is partly driven by aging populations and improved diagnostics; nevertheless, it also reflects an increase in the true incidence of hematologic malignancies. This growing burden is especially concerning in lower-income countries, where the incidence is rising steeply despite limited access to treatment modalities. Beyond mortality, this leads to a significantly worse quality of life [ 3 ], financial toxicity [ 4 , 5 ], and disability [ 6 ]. The pathogenesis of hematologic malignancies remains an enigma, underscoring the need to better characterize potentially modifiable environmental contributors.

Air pollution is defined as the presence of substances in the air at concentrations or durations higher than naturally expected, with the potential to adversely affect health [ 7 ]. Outdoor Air Pollution (OAP) consists of a combination of liquid, gaseous, and solid particles suspended in the atmosphere. This mixture includes pollutants like carbon monoxide (CO), lead (Pb), nitrogen dioxide (NO 2 ), ozone (O 3 ), particulate matter (PM), and sulfur dioxide (SO 2 ) [ 8 ]. Given this heterogenous mixture of pollutants, each with distinct toxicologic properties, associations observed with overall OAP exposure may reflect the contribution of the individual components and correlated exposures rather than a uniform biologic effect. OAP is well known for its association with respiratory disorders and lung cancer; however, it has far-reaching health consequences involving multiple organ systems [ 9 ]. According to the 2021 Global Burden of Disease (GBD) [ 10 ] data, particulate matter air pollution was responsible for 8% of total disability-adjusted life years (DALY) lost, making it the leading contributor to GBD, surpassing other risk factors like smoking, hypertension, and diabetes. It is now considered one of the greatest environmental threats to human health, with 13 attributed deaths every minute worldwide [ 11 ]. Ambient (outdoor) air pollution led to 4.2 million premature deaths in 2019, 89% of which were in low and middle-income countries. When accounting for household (indoor) air pollution, the number totals to 6.7 million [ 12 ].

An association between environmental pollutants and cancer has been debated since the 1950s, when many studies showed an urban-rural divide in lung cancer incidence, even after accounting for cigarette smoking [ 13 ]. It was officially classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) in 2013 [ 14 ]. Among solid tumors, other reported associations are with genitourinary malignancies [ 15 , 16 ], including bladder, kidney, and prostate cancers, breast cancer [ 17 – 19 ], and gastrointestinal malignancies [ 20 , 21 ].

There is a growing body of evidence that this association may extend beyond solid tumors. In 2018, the IARC concluded that exposure to benzene was associated with an increase in the risk of Acute Myeloid Leukemia (AML), with limited but positive data for Acute Lymphoblastic Leukemia (ALL) and non-Hodgkin lymphomas (NHL) in adults [ 22 ]. A Danish case-control study found that NO 2 increased the risk of AML in an adult population [ 23 ]. Another recent study by Diver et al. [ 24 ] found correlations between individual pollutants and specific types of lymphomas. OAP was associated with increased mortality from hematologic malignancies in a large cohort of US adults [ 25 ]. Other studies have shown mixed results [ 26 – 30 ], possibly owing to the heterogeneity of hematologic malignancies, with variable disease biology. To our knowledge, a single systematic review and dose-response meta-analysis has been completed on this topic by Lin et al. [ 31 ] in 2023, who reported sustained significant associations of OAP exposure with hematologic malignancies, modified by age, disease subtype, and geographic region.

With this review, we aim to provide an updated perspective on the epidemiologic evidence linking air pollution to the different subtypes of hematologic malignancies with a focus on the molecular mechanisms of carcinogenesis. We also address disparities, the human and economic toll of the rising burden of hematologic malignancies, as well as the importance of public policy in combating air pollution.

Air Pollutants and Molecular Mechanisms of Carcinogenesis

Particulate Matter (PM 2.5 and PM 10 )

Exposure to airborne particulate matter (PM) contributes to carcinogenesis through multiple mechanisms of DNA damage. PM consists of airborne solid particles and liquid droplets stratified by size [ 32 ]. PM 10 includes particles ≤ 10 μm in diameter, including dust, pollen, and mold, whereas PM 2.5 refers to fine particulate matter < 2.5 μm derived from natural and anthropogenic sources such as industrial emissions and fossil fuel combustion. Their smaller size allows PM 2.5 particles to penetrate the respiratory tract and enter systemic circulation [ 33 , 34 ]. PM 2.5 exposure is associated with increased reactive oxygen species (ROS) generation, oxidative DNA damage, and methylated DNA adduct formation [ 33 , 34 ]. In human myeloid leukemia cells, low-dose PM2.5 exposure increased ROS levels, inflammatory markers including IL-6 and COX-2, inflammatory gene expression, and leukemia cell growth in vitro and in vivo [ 35 ]. Black carbon/PM 2.5 exposure promotes IL-1β-mediated inflammation, alters hematopoietic progenitor dynamics, and enhances expansion of TET2-mutant clones, supporting a role in myeloid carcinogenesis [ 36 ].

Compared with PM 2.5 , PM 10 exposure is associated with a greater burden of genomic alterations and DNA repair-related mutational signatures, whereas PM 2.5 is more strongly associated with oxidative stress-related signatures [ 37 ]. Persistent oxidative stress and epigenetic dysregulation, including hypermethylation of tumor suppressor genes, contribute to malignant transformation in hematopoietic and other tissues [ 38 ].

Benzene

Benzene is a well-established environmental and occupational toxin associated with bone marrow toxicity and leukemia risk [ 39 ]. It is primarily emitted from coal and oil industries, motor vehicle exhaust, and tobacco smoke [ 40 ]. Genomic analyses of benzene-exposed workers identified alterations in genes involved in immune signaling, DNA repair, and cell survival, including NFKB1, along with dose-dependent DNA methylation changes and altered miRNA regulation indicative of persistent epigenetic reprogramming [ 41 ]. Benzene-associated molecular signatures overlapped significantly with those of AML, suggesting a role in early leukemogenic changes in hematopoietic progenitor cells prior to overt malignancy [ 41 ]. Cytogenetic studies further demonstrated similarities between benzene-associated AML and de novo AML [ 42 ]. These findings support experimental data showing that benzene metabolites induce oxidative stress, DNA damage, and disruption of hematopoietic stem and progenitor cell function, leading to impaired hematopoiesis and clonal malignant transformation.

Arsenic

Arsenic, an element emitted by high-temperature processes such as coal-fired power plants and burning vegetation [ 43 ], disrupts early hematopoiesis through multiple mechanisms. Medina et al. demonstrated that arsenite exposure impairs early hematopoiesis by reducing the binding capability of transcription factor GATA-2 to regulatory DNA elements, disrupting hematopoietic differentiation, and promoting accumulation of immature progenitor cells [ 44 ]. Chronic low-level arsenic exposure aberrantly activates the PI3K/Akt signaling pathway, promoting survival and proliferation of hematopoietic progenitors while impairing apoptotic checkpoints [ 45 ]. Interestingly, arsenic also serves as a therapeutic modality in acute promyelocytic leukemia, highlighting its paradoxical capacity to exert both pro- and anti-carcinogenic effects. Further studies are needed to better characterize the exposure contexts, molecular pathways, and biologic conditions underlying these divergent effects.

Ethylene Oxide (EtO)

EtO, a Group 1 carcinogen emitted by industrial and sterilization sites, is a direct alkylating agent with a well-characterized genotoxic mechanism [ 46 ]. Walker et al. demonstrated in murine models that inhaled EtO forms covalent DNA adducts in a dose-dependent manner across multiple tissues [ 47 ]. These adducts persist due to incomplete DNA repair, promoting mutational accumulation during replication. The continuous division of hematopoietic stem and progenitor cells likely increases their vulnerability to clonal expansion and malignant transformation. These mechanistic findings support epidemiologic evidence linking occupational EtO exposure to increased leukemia and lymphoma risk.

Nitrogen Dioxide (NO 2 )

NO 2 is primarily emitted through fossil fuel combustion from vehicles, power plants, industrial facilities, household appliances, and tobacco smoke [ 48 ]. NO₂ is a reactive free-radical gas that enters systemic circulation and generates ROS, overwhelming cellular antioxidant defenses, causing DNA strand breaks, DNA-protein crosslinks, and the formation of micronuclei in bone marrow cells [ 49 ]. NO₂ further impairs cellular function and promotes chronic inflammation through protein nitration (e.g., nitrotyrosine formation) [ 50 ]. Cumulative genotoxicity, persistent oxidative stress, and long-term immune dysregulation contribute to malignant cellular transformation. However, as NO 2 is frequently studied alongside other pollutants such as PM 2.5 and benzene, isolating NO 2 ’s independent contribution to hematologic malignancy remains challenging.

Sulfur Dioxide (SO 2 )

SO 2 is an air pollutant with significant carcinogenic potential. Upon inhalation, SO 2 hydrates in the airways to form sulfurous acid, dissociating into bisulfite and sulfite ions that enter systemic circulation and distribute to multiple organs, including the bone marrow [ 51 , 52 ]. SO 2 is associated with direct DNA damage, as evidenced by a higher frequency of chromosome aberrations, sister-chromatid exchanges, and micronuclei formation across humans, murine, and in-vitro models [ 52 – 55 ]. It also acts as a co-carcinogen [ 56 ] by depleting cellular glutathione [ 57 ], enhancing pollutant-DNA binding [ 56 ], activating procarcinogens into their carcinogenic metabolites [ 58 ], and potentiating the mutagenicity of co-pollutants such as particulate matter [ 59 ]. Additionally, SO 2 upregulates proto-oncogenes and downregulates tumor suppressor genes relevant to hematologic malignancies, including c-myc, p53, p16, and Rb [ 60 ]. Epidemiologically, SO 2 exposure demonstrates a dose-response relationship with non-Hodgkin lymphoma (NHL) incidence and has been linked to increased mortality from leukemias and NHL among pulp and paper industry workers [ 61 ], though further research is needed to characterize its effects at ambient exposure levels on the general population (Fig. 1 ).

Fig. 1 Molecular Mechanisms of Carcinogenesis. Created in BioRender. Murli, H. (2026) https://BioRender.com/tkhy5k7

Epidemiological Evidence Linking Air Pollution and Hematologic Malignancies

A landmark cohort of Pliofilm rubber workers provided foundational epidemiologic evidence establishing benzene as a leukemogen, particularly in relation to acute myeloid leukemia (AML) [ 62 , 63 ]. While early studies focused on high-dose occupational exposure, subsequent research has increasingly explored lower-level environmental exposure in the general population [ 64 , 65 ]. Occupational cohort studies demonstrated hematopoietic toxicity, including cytopenias, even at benzene exposures below 1 ppm, supporting leukemogenic potential at relatively low exposure levels [ 66 ]. Although lifetime exposures below 50 ppm-years were initially considered unlikely to significantly increase AML risk [ 67 ], later studies demonstrated elevated AML risk at substantially lower exposure levels, including among petrochemical workers exposed to 2–8 ppm-years [ 68 ]. Additional studies have reported leukemia risk following prolonged exposure to gasoline vapors after environmental spills, as well as dose-response relationships between cumulative benzene exposure and hematologic malignancies [ 69 ]. More recently, multiple population-based studies have demonstrated increased AML incidence in communities with higher ambient benzene exposure [ 70 ]. Collectively, these findings suggest leukemogenic potential even at lower environmental exposure levels.

The strength of epidemiologic evidence linking outdoor air pollution to hematologic malignancies varies considerably across disease entities. While the association between benzene exposure and AML is supported by extensive occupational, environmental, and mechanistic evidence, associations involving MDS, CHIP, and specific lymphoma subtypes are supported by a smaller but growing body of literature. In contrast, evidence linking ambient air pollution to chronic leukemias and multiple myeloma remains limited and inconsistent. Accordingly, the epidemiologic literature is discussed below according to the strength of the available evidence rather than by disease category alone (Table 1 ).

Table 1 Strength of epidemiologic evidence linking outdoor air pollution to hematologic malignancies Strength of Evidence Hematologic Malignancy Pollutant(s) Summary of Evidence Strong AML Benzene Consistent occupational, environmental, dose-response, cohort, and meta-analytic evidence supports the strongest epidemiological association Childhood acute leukemias Traffic-related pollution Multiple studies and a meta-analysis demonstrate increased risk, although individual pollutants are less consistent Emerging ALL Benzene, PM 2.5 , NO 2 Evidence suggests increased risk, particularly in childhood disease, although results are heterogeneous across pollutants. Lymphomas PM, NO 2 , CO, Benzene Associations appear subtype-specific (mantle cell, marginal zone, Hodgkin lymphoma) rather than consistent across all lymphomas. MDS Benzene, PM 2.5 Several occupational and recent population and experimental studies suggest increased risk, but the literature remains relatively limited. CHIP PM 2.5 Multiple recent studies suggest increased CHIP prevalence and clonal burden, although the relationship with subsequent hematologic malignancy remains uncertain. Limited or Uncertain CLL PM 2.5 , Benzene, 1,3-butadiene Findings are inconsistent, with predominantly null meta-analytic evidence. CML Benzene Few studies available; evidence remains insufficient. Multiple Myeloma PM 2.5 , NO 2 , O 3 Incidence studies largely negative, although PM exposure may adversely affect survival after diagnosis.

Strong Epidemiologic Evidence

Benzene and AML

With advances in exposure assessment methods, individual pollutants have increasingly been investigated. Among them, benzene demonstrates the strongest association with AML. A case-control study in Oklahoma found that children with AML had approximately threefold higher benzene exposure than controls [ 71 ], while prenatal benzene exposure has also been associated with increased childhood AML risk [ 72 ]. Lin et al. reported a pooled relative risk of 1.84 for AML with benzene exposure [ 31 ]. Although many studies combine occupational, household, and ambient exposures, limiting isolation of environmental effects alone [ 73 ], benzene exposure demonstrates a dose-dependent relationship with both AML and ALL, with stronger and more consistent associations observed for AML [ 73 , 74 ].

Traffic-related Pollution and Acute Leukemias

OAP has increasingly been associated with acute leukemias, although the magnitude of risk appears to vary according to pollutant composition, exposure setting, and critical windows of exposure. Early epidemiologic studies used traffic density as a surrogate marker for OAP exposure and consistently demonstrated elevated leukemia risk in children living near high-traffic areas. In the French GEOCAP study, proximity to high-traffic roads was associated with a 1.2-fold higher risk of AML [ 75 ], while a Spanish study reported a threefold increase in leukemia risk [ 76 ]. Meta-analyses have since confirmed a modest but significant association between traffic-related pollution and acute leukemia risk [ 31 , 74 ]. Collectively, epidemiologic studies and meta-analyses support a consistent association between traffic-related air pollution and childhood acute leukemias, although the specific pollutant(s) responsible remain less clearly defined than for benzene-associated AML.

Emerging Epidemiologic Evidence

NO 2 and Acute Leukemias

The epidemiologic evidence for NO₂ and particulate matter is comparatively less consistent. Some studies have demonstrated stronger associations between NO₂ exposure and ALL, particularly at exposure levels exceeding 40 µg/m³, whereas others reported stronger associations with AML [ 77 , 78 ]. Prenatal exposure to nitrogen oxides has also been associated with increased ALL risk [ 79 ]. Meta-analyses have not consistently demonstrated significant associations between NO₂ exposure and acute leukemia overall, although dose-response relationships and regional variation, with over two-fold increase in acute leukemia risk in Asian populations, have been reported [ 31 ].

PM and Acute Leukemias

PM 2.5 exposure demonstrates heterogeneous associations with acute leukemias [ 31 ]. Prenatal exposure to PM, particularly PM 10 , was associated with increased childhood leukemia risk in a Spanish study [ 80 ]. A Danish registry study found increased leukemia risk with PM 2.5 exposure over 1-, 5-, and 10-year exposure periods, with the strongest effect observed in adults older than 70 years [ 81 ]. PM 2.5 exposure in Denmark remained associated with increased leukemia odds even in multi-pollutant models [ 29 ]. However, other studies have reported null associations [ 82 ].

Several studies suggest a stronger relationship between PM exposure and ALL. A Texas study demonstrated increased ALL incidence in children living in counties with PM 2.5 concentrations exceeding Environmental Protection Agency (EPA) standards, particularly among Hispanic children [ 83 ]. A Mexican study similarly identified clusters of increased ALL incidence correlating with higher PM 2.5 levels [ 84 ]. In contrast, fewer studies have specifically examined AML, with the Danish registry study remaining among the most notable positive studies [ 81 ]. Despite these findings, the Lin et al. meta-analysis did not demonstrate statistically significant associations between PM exposure and either ALL or AML [ 31 ]. Additional pollutants, including 1,3-butadiene and ozone, have also demonstrated possible associations with childhood leukemia risk in isolated studies [ 85 , 86 ].

Lymphomas

The US-based study by Diver et al. remains one of the more robust analyses of OAP and lymphoma risk. Higher PM 10−2.5 concentrations were associated with increased risk of mantle cell lymphoma (HR 1.43 per 4.1 µg/m 3 increase) [ 24 ]. Hodgkin lymphoma (HL) was associated with NO 2 exposure, T-cell lymphoma with CO exposure, and marginal zone lymphoma with both NO 2 and CO exposure, with hazard ratios of approximately 1.3 [ 24 ]. However, findings across lymphoma subtypes remain inconsistent. A large population-based study found no significant associations between multiple pollutants, including PM 2.5 , O 3 , SO 2 , and NO 2 , and NHL overall [ 87 ], although some pollutants demonstrated non-significant elevations in follicular lymphoma risk. Other studies similarly found no association between OAP and HL or NHL overall, though PM constituents were associated with follicular lymphoma in some analyses [ 30 , 87 , 88 ].

Prenatal exposure to NO 2 and benzene has also been associated with increased HL risk, with one study demonstrating a significant dose-response relationship for NO 2 exposure [ 89 ]. Additional environmental exposures linked to lymphoma risk include proximity to paper industries, solid waste incinerators, and dioxin exposure [ 90 – 92 ]. Overall, meta-analytic data demonstrate predominantly null associations between most pollutants and lymphoma risk, although notable exceptions include strong associations between benzene exposure and HL, as well as between PM 2.5 exposure and adolescent NHL [ 31 ].

MDS

Vicinity to industrial plants and lifetime oil exposure are linked to a higher risk of MDS, along with specific occupations [ 93 ]. Low-level benzene exposure among petroleum workers demonstrated a monotonic dose-response relationship with MDS, notably without a corresponding association with AML, suggesting that MDS may be a more relevant entity at lower exposure levels, such as those encountered in OAP [ 94 ]. Occupational and environmental exposures are associated with abnormal cytogenetics in MDS [ 95 ]. More recently, long-term PM 2.5 exposure was associated with increased incident MDS risk and higher-risk MDS phenotypes in a Bronx-based study [ 36 ].

Clonal Hematopoiesis of Indeterminate Potential

The most comprehensive study on Clonal Hematopoiesis of Indeterminate Potential (CHIP) and OAP comes from the 2024 study by Aboshahem et al., involving genotyping of over 7000 patients, which found not only an increased risk of CHIP with higher PM 2.5 concentrations, but also an increased number of CHIP mutations. PM 2.5 exposure also increased the risk of major cardiovascular events in patients with CHIP mutations [ 96 ]. The landmark study by Jasra et al., following first responders involved in the World Trade Center (WTC) tragedy, found increased rates of CHIP mutations with an odds ratio of over 3, in cases that were exposed to WTC PM, compared to controls [ 97 ]. Somatic mutations in DNMT3A and TET2 were increased. In contrast, a 2023 epidemiologic study found a positive but non-significant association between OAP, specifically PM 2.5 and NO 2 , and risk of CHIP, likely limited by low power [ 98 ]. It is important to note that the association of pollution-associated CHIP and hematologic malignancy remains uncertain, especially given strong lifestyle factors such as age, smoking, and occupational hazards increasing inflammation. However, these findings do suggest that exposure to environmental toxins and gases can potentially influence early clonal evolution and CHIP.

Limited or Uncertain Epidemiologic Evidence

Chronic Leukemias

Evidence linking OAP to chronic leukemias remains limited and less consistent than for acute leukemias. The Danish registry study by Puett et al. demonstrated an increased risk of CLL with higher 1-year average PM 2.5 exposure [ 81 ]. In contrast, a Canadian case-control study found no significant associations between NO 2 or PM 2.5 exposure and CLL [ 28 ]. Although an inverse relationship was observed, this finding is unlikely to be causal, given the biologic implausibility, and may instead reflect residual confounding or underdiagnosis of an indolent malignancy in lower-resource, high-exposure regions.

Evidence linking benzene exposure to chronic leukemias is similarly limited. Older occupational case reports suggested possible associations [ 99 ], but subsequent occupational case-control studies did not demonstrate significant associations between benzene exposure and either CLL or CML [ 100 ]. Given that occupational exposures are typically substantially higher than environmental exposures, these findings may argue against a strong association between ambient benzene exposure and chronic leukemias. In contrast, 1,3-butadiene has shown more consistent associations with lymphoid malignancies, particularly CLL [ 101 ].

Meta-analytic data remain limited by the small number of available studies. Lin et al. were unable to generate pooled risk estimates for several pollutants in CLL because of insufficient data, while pooled estimates for NO 2 , PM 2.5 , and O 3 were not statistically significant [ 31 ]. Similar limitations exist for CML, where epidemiologic evidence remains largely restricted to occupational studies [ 31 , 102 ]. Although meta-analyses have not demonstrated significant associations, some studies suggest stronger associations in higher-quality and more recent cohorts [ 102 ].

Multiple Myeloma

A large European study with over 200,000 participants showed no association between OAP and the risk of MM. Pollutants studied included NO 2 , PM 2.5 , black carbon, and O 3 [ 103 ]. However, the number of years of PM 2.5 exposure above EPA and Word Health Organization standards was associated with lower overall survival in MM patients in a study involving over 1500 participants [ 104 ]. Self-reported exposure to CO, along with other toxic compounds, was found to increase the risk of MM in another study; however, occupational exposures were included [ 105 ]. Diesel exhaust was not associated with elevated MM risk based on a review of existing studies [ 106 ]. Meta-analysis was limited by meager data, but found null associations for all pollutants studied [ 31 ].

Disparities, Societal Burden, and Public Health Implications

OAP is not a homogenously distributed risk factor, and there is considerable variation in exposure rates globally, within countries, and even within individual cities. In the United States, significant geographic disparities in OAP exposure persist despite overall improvements in air quality over recent decades [ 107 ]. These disparities are inextricably linked to socioeconomic and racial factors, with racial and ethnic minorities disproportionately more likely to live near industrial plants and hazardous waste incinerators [ 108 , 109 ]. Analysis of PM 2.5 exposure data in the United States from 2000 to 2016 demonstrated consistently higher concentrations in communities with larger Black, Hispanic, and Asian populations, whereas predominantly White neighborhoods generally experienced lower exposure levels [ 110 ]. Low-income communities may also face modestly higher pollutant exposure burdens [ 109 , 110 ].

In recent years, OAP has emerged as a crucial concern in rapidly developing countries [ 111 ]. Industrialization comes with its environmental costs, especially when a conscious investment is not made into sustainable energy sources. The chemical constituents of OAP may be vastly different in developing countries, leading to varying health effects. Indoor air pollution due to traditional cooking fuels also becomes a much larger consideration compared to developed countries [ 112 ]. There is a substantial need for more OAP research in these countries to identify and combat unique challenges.

As the global burden of hematologic malignancies continues to rise, so do their individual and societal consequences. Beyond morbidity and mortality, these diseases impose substantial direct and indirect financial burdens on patients, caregivers, and healthcare systems. High insurance-related expenses and out-of-pocket (OOP) costs contribute significantly to financial hardship, particularly in acute myeloid leukemia (AML), where annual OOP costs may exceed $7,000 [ 113 ]. Although advances such as chimeric antigen receptor T-cell (CAR-T) therapy and allogeneic hematopoietic stem cell transplantation (HSCT) have improved outcomes, they often further increase long-term financial strain [ 114 – 116 ]. Patients also experience major indirect costs, including loss of productivity and disability after treatment [ 117 ]. Collectively, these economic and psychosocial consequences have been termed the “financial toxicity” of cancer care [ 118 ].

The financial burden of hematologic malignancies also extends to caregivers, who frequently experience reduced productivity and employment disruptions while providing care [ 119 ]. Cancer survivors demonstrate lower long-term employment rates, contributing to substantial societal productivity losses [ 120 , 121 ]. Hematologic malignancies additionally impose disproportionately high healthcare expenditures compared with many other cancers, driven in part by resource-intensive therapies such as allogeneic hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell (CAR-T) therapy [ 115 , 122 – 124 ]. In a 2017 study, the cost of a single patient’s treatment across three years following an acute leukemia diagnosis was estimated to be over $800,000 USD, compared to $250,000 for lung cancer and under $150,000 for colorectal cancer [ 122 ]. Consequently, public health policies aimed at reducing air pollution may provide not only health benefits, but also meaningful economic benefits for patients, caregivers, healthcare systems, and society as a whole.

Conclusion

Our review demonstrates strong mechanistic evidence supporting the biologic plausibility of OAP-induced carcinogenesis in hematologic malignancies. Although epidemiologic evidence varies across pollutants, exposure levels, and malignancy subtypes, the overall literature is highly suggestive of a significant association between OAP exposure and hematologic malignancies, particularly AML and benzene exposure. These relationships are further modified by socioeconomic and geographic disparities.

Important limitations remain in the current literature. Many studies evaluate leukemia broadly without adequately distinguishing among specific subtypes, despite substantial biologic and clinical heterogeneity. Existing epidemiologic data are largely ecological and population-based, making them susceptible to unmeasured confounding and exposure misclassification. Exposure assessment represents a particularly important limitation. Residential address is often used as a proxy for exposure, but ambient pollutant concentrations at the place of residence may not accurately reflect the entire exposome, which is also shaped by time spent at work, commuting patterns, indoor air quality, and other daily activities. Occupational exposures may exceed or otherwise confound the effects of ambient pollution, while indoor sources and building characteristics may either amplify or attenuate exposure. Residential mobility over time further complicates estimation of cumulative and latency-relevant exposures, particularly for malignancies that may develop over many years. Socioeconomic factors also influence where individuals live and work, housing quality, occupational risk, access to cleaner environments, and the likelihood of exposure to multiple pollutants, thereby contributing to exposure heterogeneity.

Older studies additionally relied on imprecise pollutant exposure models, such as EPA ASPEN [ 125 ], rather than direct pollutant measurements. Studies based on residential addresses are further limited by residential mobility over time. Moreover, the diagnostic classification of hematologic malignancies, particularly along the AML-MDS spectrum, continues to evolve, contributing to variability in outcome definitions across older and newer studies. Nonetheless, emerging evidence linking OAP exposure to entities such as MDS and CHIP highlights the need for continued mechanistic and population-based research.

The Clean Air Act was associated with 300 fewer leukemia deaths between 2020 and 2025 [ 126 ]. Although the effect of smoking cessation remains greater, reducing OAP represents an important complementary public health strategy given its widespread exposure and broad health consequences. Since OAP is a potentially modifiable environmental contributor that cannot be meaningfully addressed at the individual level alone, continued efforts from policymakers and healthcare systems are essential to improve air quality and reduce the burden of hematologic malignancies. Our role as healthcare providers is to continue researching the consequences of OAP, empower patients to advocate for cleaner air, and ourselves ardently advocate for better air quality for all.

Publisher’s Note

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Authors’ Contributions

HM: Manuscript drafting, section organization, creation of Figs. 1 and 2, project coordination, formatting, citation management, and manuscript revision.SA: Manuscript drafting and manuscript review.EM: Manuscript drafting, manuscript revision, citation management, and editorial feedback.AS: Conceptualization, supervision, project direction, and critical revision of the manuscript. AS served as the invited author for the review.All authors reviewed and approved the final manuscript.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Disclosure

In the past 2 years Aditi Shastri has received honoraria for educational activities from Great Debates, MJHLS, HemeOnc Pulse and Geron. Advisory board fees from Geron, Ryvu Therapeutics, Caris Lifesciences. Research funding from Kymera Therapeutics and Ryvu Therapeutics and is Data Safety Monitoring Board Chair for Servier Pharmaceuticals.

Competing interests

The authors declare no competing interests.

References

1. Zhang N Wu J Wang Q Liang Y Li X Chen G Global burden of hematologic malignancies and evolution patterns over the past 30 years Blood Cancer J 2023 13 82 10.1038/s41408-023-00853-3 37193689 PMC10188596 Zhang N, Wu J, Wang Q, Liang Y, Li X, Chen G, et al. Global burden of hematologic malignancies and evolution patterns over the past 30 years. Blood Cancer J. 2023;13:82. 10.1038/s41408-023-00853-3. 37193689 10.1038/s41408-023-00853-3 PMC10188596

2. Shen Z Huang L Xing X Zhang D Cai G Sang W Global Burden of Hematologic Malignancies From 1990 to 2021 With Projections to 2030: A Systematic Analysis for the Global Burden of Disease Study 2021 iNew Med 2026 2 e70008 10.1002/inm3.70008 Shen Z, Huang L, Xing X, Zhang D, Cai G, Sang W. Global Burden of Hematologic Malignancies From 1990 to 2021 With Projections to 2030: A Systematic Analysis for the Global Burden of Disease Study 2021. iNew Med. 2026;2:e70008. 10.1002/inm3.70008.

3. Allart-Vorelli P Porro B Baguet F Michel A Cousson-Gélie F Haematological cancer and quality of life: a systematic literature review Blood Cancer J 2015 5 e305 305 10.1038/bcj.2015.29 25909835 PMC4450328 Allart-Vorelli P, Porro B, Baguet F, Michel A, Cousson-Gélie F. Haematological cancer and quality of life: a systematic literature review. Blood Cancer J. 2015;5:e305–305. 10.1038/bcj.2015.29. 25909835 10.1038/bcj.2015.29 PMC4450328

4. Ouchveridze E Banerjee R Desai A Aziz M Lee-Smith W Mian H Financial toxicity in hematological malignancies: a systematic review Blood Cancer J 2022 12 74 10.1038/s41408-022-00671-z 35459862 PMC9033803 Ouchveridze E, Banerjee R, Desai A, Aziz M, Lee-Smith W, Mian H, et al. Financial toxicity in hematological malignancies: a systematic review. Blood Cancer J. 2022;12:74. 10.1038/s41408-022-00671-z. 35459862 10.1038/s41408-022-00671-z PMC9033803

5. Sparano F Giesinger JM Gaidano G Anota A Cavo M Brini A Financial toxicity and health-related quality of life profile of patients with hematologic malignancies treated in a universal health care system JCO Oncol Pract 2024 20 438 47 10.1200/OP.23.00434 38207239 Sparano F, Giesinger JM, Gaidano G, Anota A, Cavo M, Brini A, et al. Financial toxicity and health-related quality of life profile of patients with hematologic malignancies treated in a universal health care system. JCO Oncol Pract. 2024;20:438–47. 10.1200/OP.23.00434. 38207239 10.1200/OP.23.00434

6. Li Y Jia C Sun T Zhang L Yang R Global Burden and Disparities in Hematologic Malignancies: A Comparative Analysis from 1990 to 2019 Blood 2023 142 7280 10.1182/blood-2023-173597 Li Y, Jia C, Sun T, Zhang L, Yang R. Global Burden and Disparities in Hematologic Malignancies: A Comparative Analysis from 1990 to 2019. Blood. 2023;142:7280. 10.1182/blood-2023-173597.

7. International Agency for Research on Cancer. Definition of outdoor air pollution. In: Outdoor air pollution [Internet]. Lyon: IARC. 2016. Available from: https://www.ncbi.nlm.nih.gov/books/NBK368034/ . Accessed 2026 Apr 8.

8. US Environmental Protection Agency. Outdoor air quality [Internet]. 2017. Available from: https://www.epa.gov/report-environment/outdoor-air-quality . Accessed 2026 Apr 8.

9. Schraufnagel DE Balmes JR Cowl CT Matteis SD Jung S-H Mortimer K Air Pollution and Noncommunicable Diseases: A Review by the Forum of International Respiratory Societies’ Environmental Committee, Part 2: Air Pollution and Organ Systems Chest 2019 155 417 26 10.1016/j.chest.2018.10.041 30419237 PMC6904854 Schraufnagel DE, Balmes JR, Cowl CT, Matteis SD, Jung S-H, Mortimer K, et al. Air Pollution and Noncommunicable Diseases: A Review by the Forum of International Respiratory Societies’ Environmental Committee, Part 2: Air Pollution and Organ Systems. Chest. 2019;155:417–26. 10.1016/j.chest.2018.10.041. 30419237 10.1016/j.chest.2018.10.041 PMC6904854

10. Brauer M Roth GA Aravkin AY Zheng P Abate KH Abate YH Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 Lancet 1990 403 2162 203 10.1016/S0140-6736(24)00933-4 PMC11120204 38762324 Brauer M, Roth GA, Aravkin AY, Zheng P, Abate KH, Abate YH, et al. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 1990;403:2162–203. 10.1016/S0140-6736(24)00933-4. 10.1016/S0140-6736(24)00933-4 PMC11120204 38762324

11. World Health Organization. Air pollution [Internet]. Available from: https://www.who.int/health-topics/air-pollution . Accessed 2025 Mar 31.

12. World Health Organization. Ambient (outdoor) air pollution [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/ambient-(outdoor)-air-quality-and-health . Accessed 2025 Mar 31.

13. Cohen AJ Pope CA Lung cancer and air pollution Environ Health Perspect 1995 103 219 24 10.1289/ehp.95103s8219 8741787 PMC1518961 Cohen AJ, Pope CA. Lung cancer and air pollution. Environ Health Perspect. 1995;103:219–24. 10.1289/ehp.95103s8219. 8741787 10.1289/ehp.95103s8219 PMC1518961

14. International Agency for Research on Cancer. Outdoor air pollution a leading environmental cause of cancer deaths [Internet]. Available from: https://www.iarc.who.int/news-events/iarc-outdoor-air-pollution-a-leading-environmental-cause-of-cancer-deaths . Accessed 2025 Mar 31.

15. Zare Sakhvidi MJ Lequy E Goldberg M Jacquemin B Air pollution exposure and bladder, kidney and urinary tract cancer risk: A systematic review Environ Pollut 2020 267 115328 10.1016/j.envpol.2020.115328 32871482 Zare Sakhvidi MJ, Lequy E, Goldberg M, Jacquemin B. Air pollution exposure and bladder, kidney and urinary tract cancer risk: A systematic review. Environ Pollut. 2020;267:115328. 10.1016/j.envpol.2020.115328. 32871482 10.1016/j.envpol.2020.115328

16. Li J Deng Z Soerensen SJC Kachuri L Cardenas A Graff RE Ambient air pollution and urological cancer risk: A systematic review and meta-analysis of epidemiological evidence Nat Commun 2024 15 5116 10.1038/s41467-024-48857-2 38879581 PMC11180144 Li J, Deng Z, Soerensen SJC, Kachuri L, Cardenas A, Graff RE, et al. Ambient air pollution and urological cancer risk: A systematic review and meta-analysis of epidemiological evidence. Nat Commun. 2024;15:5116. 10.1038/s41467-024-48857-2. 38879581 10.1038/s41467-024-48857-2 PMC11180144

17. Wei Y Davis J Bina WF Ambient air pollution is associated with the increased incidence of breast cancer in US Int J Environ Health Res 2012 22 12 21 10.1080/09603123.2011.588321 21644128 Wei Y, Davis J, Bina WF. Ambient air pollution is associated with the increased incidence of breast cancer in US. Int J Environ Health Res. 2012;22:12–21. 10.1080/09603123.2011.588321. 21644128 10.1080/09603123.2011.588321

18. Hystad P Villeneuve PJ Goldberg MS Crouse DL Johnson K Exposure to traffic-related air pollution and the risk of developing breast cancer among women in eight Canadian provinces: a case–control study Environ Int 2015 74 240 8 10.1016/j.envint.2014.09.004 25454241 Hystad P, Villeneuve PJ, Goldberg MS, Crouse DL, Johnson K. Exposure to traffic-related air pollution and the risk of developing breast cancer among women in eight Canadian provinces: a case–control study. Environ Int. 2015;74:240–8. 10.1016/j.envint.2014.09.004. 25454241 10.1016/j.envint.2014.09.004

19. Gabet S Lemarchand C Guénel P Slama R Breast cancer risk in association with atmospheric pollution exposure: a meta-analysis of effect estimates followed by a health impact assessment Environ Health Perspect 2021 129 057012 10.1289/EHP8419 34038220 PMC8153692 Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: a meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:057012. 10.1289/EHP8419. 34038220 10.1289/EHP8419 PMC8153692

20. Pritchett N Spangler EC Gray GM Livinski AA Sampson JN Dawsey SM Exposure to Outdoor Particulate Matter Air Pollution and Risk of Gastrointestinal Cancers in Adults: A Systematic Review and Meta-Analysis of Epidemiologic Evidence Environ Health Perspect 2022 130 036001 10.1289/EHP9620 35234536 PMC8890324 Pritchett N, Spangler EC, Gray GM, Livinski AA, Sampson JN, Dawsey SM, et al. Exposure to Outdoor Particulate Matter Air Pollution and Risk of Gastrointestinal Cancers in Adults: A Systematic Review and Meta-Analysis of Epidemiologic Evidence. Environ Health Perspect. 2022;130:036001. 10.1289/EHP9620. 35234536 10.1289/EHP9620 PMC8890324

21. Guo C Chan T-C Teng Y-C Lin C Bo Y Chang L Long-term exposure to ambient fine particles and gastrointestinal cancer mortality in Taiwan: A cohort study Environ Int 2020 138 105640 10.1016/j.envint.2020.105640 32179321 Guo C, Chan T-C, Teng Y-C, Lin C, Bo Y, Chang L, et al. Long-term exposure to ambient fine particles and gastrointestinal cancer mortality in Taiwan: A cohort study. Environ Int. 2020;138:105640. 10.1016/j.envint.2020.105640. 32179321 10.1016/j.envint.2020.105640

22. International Agency for Research on Cancer Summary of data reported Benzene [Internet] 2018 Lyon IARC International Agency for Research on Cancer. Summary of data reported. In: Benzene [Internet]. Lyon: IARC; 2018.

23. Raaschou-Nielsen O Ketzel M Harbo Poulsen A Sørensen M Traffic‐related air pollution and risk for leukaemia of an adult population Int J Cancer 2016 138 1111 7 10.1002/ijc.29867 26415047 Raaschou-Nielsen O, Ketzel M, Harbo Poulsen A, Sørensen M. Traffic‐related air pollution and risk for leukaemia of an adult population. Int J Cancer. 2016;138:1111–7. 10.1002/ijc.29867. 26415047 10.1002/ijc.29867

24. Diver WR Teras LR Deubler EL Turner MC Outdoor air pollution and risk of incident adult haematologic cancer subtypes in a large US prospective cohort Br J Cancer 2024 131 149 58 10.1038/s41416-024-02718-3 38802672 PMC11231250 Diver WR, Teras LR, Deubler EL, Turner MC. Outdoor air pollution and risk of incident adult haematologic cancer subtypes in a large US prospective cohort. Br J Cancer. 2024;131:149–58. 10.1038/s41416-024-02718-3. 38802672 10.1038/s41416-024-02718-3 PMC11231250

25. Coleman NC Burnett RT Higbee JD Lefler JS Merrill RM Ezzati M Cancer mortality risk, fine particulate air pollution, and smoking in a large, representative cohort of US adults Cancer Causes Control 2020 31 767 76 10.1007/s10552-020-01317-w 32462559 Coleman NC, Burnett RT, Higbee JD, Lefler JS, Merrill RM, Ezzati M, et al. Cancer mortality risk, fine particulate air pollution, and smoking in a large, representative cohort of US adults. Cancer Causes Control. 2020;31:767–76. 10.1007/s10552-020-01317-w. 32462559 10.1007/s10552-020-01317-w

26. Turner MC Krewski D Diver WR Pope CA Burnett RT Jerrett M Ambient Air Pollution and Cancer Mortality in the Cancer Prevention Study II Environ Health Perspect 2017 125 087013 10.1289/EHP1249 28886601 PMC5783657 Turner MC, Krewski D, Diver WR, Pope CA, Burnett RT, Jerrett M, et al. Ambient Air Pollution and Cancer Mortality in the Cancer Prevention Study II. Environ Health Perspect. 2017;125:087013. 10.1289/EHP1249. 28886601 10.1289/EHP1249 PMC5783657

27. Raaschou-Nielsen O Andersen ZJ Hvidberg M Jensen SS Ketzel M Sørensen M Air pollution from traffic and cancer incidence: a Danish cohort study Environ Health 2011 10 67 10.1186/1476-069X-10-67 21771295 PMC3157417 Raaschou-Nielsen O, Andersen ZJ, Hvidberg M, Jensen SS, Ketzel M, Sørensen M, et al. Air pollution from traffic and cancer incidence: a Danish cohort study. Environ Health. 2011;10:67. 10.1186/1476-069X-10-67. 21771295 10.1186/1476-069X-10-67 PMC3157417

28. Winters N Goldberg MS Hystad P Villeneuve PJ Johnson KC Canadian Cancer Registries Epidemiology Group Exposure to ambient air pollution in Canada and the risk of adult leukemia Sci Total Environ 2015 526 153 76 10.1016/j.scitotenv.2015.03.149 25955692 Winters N, Goldberg MS, Hystad P, Villeneuve PJ, Johnson KC, Canadian Cancer Registries Epidemiology Group. Exposure to ambient air pollution in Canada and the risk of adult leukemia. Sci Total Environ. 2015;526:153–76. 10.1016/j.scitotenv.2015.03.149. 25955692 10.1016/j.scitotenv.2015.03.149

29. Taj T Poulsen AH Ketzel M Geels C Brandt J Christensen JH Exposure to PM2.5 constituents and risk of adult leukemia in Denmark: a population-based case-control study Environ Res 2021 196 110418 10.1016/j.envres.2020.110418 33157111 Taj T, Poulsen AH, Ketzel M, Geels C, Brandt J, Christensen JH, et al. Exposure to PM2.5 constituents and risk of adult leukemia in Denmark: a population-based case-control study. Environ Res. 2021;196:110418. 10.1016/j.envres.2020.110418. 33157111 10.1016/j.envres.2020.110418

30. Taj T Poulsen AH Ketzel M Geels C Brandt J Christensen JH Long-term residential exposure to air pollution and Hodgkin lymphoma risk among adults in Denmark: a population-based case-control study Cancer Causes Control 2021 32 935 42 10.1007/s10552-021-01446-w 34050843 Taj T, Poulsen AH, Ketzel M, Geels C, Brandt J, Christensen JH, et al. Long-term residential exposure to air pollution and Hodgkin lymphoma risk among adults in Denmark: a population-based case-control study. Cancer Causes Control. 2021;32:935–42. 10.1007/s10552-021-01446-w. 34050843 10.1007/s10552-021-01446-w

31. Lin K Zhou G Guo H Niu Q Guo H Song G Exposure to air pollution and risk of haematological malignancies: a systematic review and dose-response meta-analysis of epidemiologic evidence Environ Res Lett 2023 18 093001 10.1088/1748-9326/aceb7a Lin K, Zhou G, Guo H, Niu Q, Guo H, Song G, et al. Exposure to air pollution and risk of haematological malignancies: a systematic review and dose-response meta-analysis of epidemiologic evidence. Environ Res Lett. 2023;18:093001. 10.1088/1748-9326/aceb7a.

32. US Environmental Protection Agency. Particulate matter (PM) basics [Internet]. 2016. Available from: https://www.epa.gov/pm-pollution/particulate-matter-pm-basics . Accessed 2026 May 20.

33. Shukla A Bunkar N Kumar R Bhargava A Tiwari R Chaudhury K Air pollution associated epigenetic modifications: Transgenerational inheritance and underlying molecular mechanisms Sci Total Environ 2019 656 760 77 10.1016/j.scitotenv.2018.11.381 30530146 Shukla A, Bunkar N, Kumar R, Bhargava A, Tiwari R, Chaudhury K, et al. Air pollution associated epigenetic modifications: Transgenerational inheritance and underlying molecular mechanisms. Sci Total Environ. 2019;656:760–77. 10.1016/j.scitotenv.2018.11.381. 30530146 10.1016/j.scitotenv.2018.11.381

34. Quezada-Maldonado EM Sánchez-Pérez Y Chirino YI García-Cuellar CM Airborne particulate matter induces oxidative damage, DNA adduct formation and alterations in DNA repair pathways Environ Pollut 2021 287 117313 10.1016/j.envpol.2021.117313 34022687 Quezada-Maldonado EM, Sánchez-Pérez Y, Chirino YI, García-Cuellar CM. Airborne particulate matter induces oxidative damage, DNA adduct formation and alterations in DNA repair pathways. Environ Pollut. 2021;287:117313. 10.1016/j.envpol.2021.117313. 34022687 10.1016/j.envpol.2021.117313

35. Jin X-T Chen M-L Li R-J An Q Song L Zhao Y Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure Arch Toxicol 2016 90 1929 38 10.1007/s00204-015-1610-x 26486797 Jin X-T, Chen M-L, Li R-J, An Q, Song L, Zhao Y, et al. Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure. Arch Toxicol. 2016;90:1929–38. 10.1007/s00204-015-1610-x. 26486797 10.1007/s00204-015-1610-x

36. Verma M Davidsohn MP Arends CM Verma D Sahu S Pradhan K Environmental Pollution Triggers Inflammation In Vivo and is Associated With Higher Risk MDS in an Urban Cohort Am J Hematol 2026 101 346 9 10.1002/ajh.70132 41215735 Verma M, Davidsohn MP, Arends CM, Verma D, Sahu S, Pradhan K, et al. Environmental Pollution Triggers Inflammation In Vivo and is Associated With Higher Risk MDS in an Urban Cohort. Am J Hematol. 2026;101:346–9. 10.1002/ajh.70132. 41215735 10.1002/ajh.70132

37. del Real Á Santurtún A Teresa Zarrabeitia M Epigenetic related changes on air quality Environ Res 2021 197 111155 10.1016/j.envres.2021.111155 33891958 del Real Á, Santurtún A, Teresa Zarrabeitia M. Epigenetic related changes on air quality. Environ Res. 2021;197:111155. 10.1016/j.envres.2021.111155. 33891958 10.1016/j.envres.2021.111155

38. Soberanes S Gonzalez A Urich D Chiarella SE Radigan KA Osornio-Vargas A Particulate matter air pollution induces hypermethylation of the p16 promoter via a mitochondrial ROS-JNK-DNMT1 pathway Sci Rep 2012 2 275 10.1038/srep00275 22355787 PMC3281276 Soberanes S, Gonzalez A, Urich D, Chiarella SE, Radigan KA, Osornio-Vargas A, et al. Particulate matter air pollution induces hypermethylation of the p16 promoter via a mitochondrial ROS-JNK-DNMT1 pathway. Sci Rep. 2012;2:275. 10.1038/srep00275. 22355787 10.1038/srep00275 PMC3281276

39. Snyder R Leukemia and Benzene Int J Environ Res Public Health 2012 9 2875 93 10.3390/ijerph9082875 23066403 PMC3447593 Snyder R. Leukemia and Benzene. Int J Environ Res Public Health. 2012;9:2875–93. 10.3390/ijerph9082875. 23066403 10.3390/ijerph9082875 PMC3447593

40. National Cancer Institute. Benzene - cancer-causing substances [Internet]. 2015. Available from: https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/benzene . Accessed 2026 May 20.

41. Vivarelli S Sevim C Giambò F Fenga C Integrated Computational Analysis Reveals Early Genetic and Epigenetic AML Susceptibility Biomarkers in Benzene-Exposed Workers Int J Mol Sci 2025 26 1138 10.3390/ijms26031138 39940906 PMC11818736 Vivarelli S, Sevim C, Giambò F, Fenga C. Integrated Computational Analysis Reveals Early Genetic and Epigenetic AML Susceptibility Biomarkers in Benzene-Exposed Workers. Int J Mol Sci. 2025;26:1138. 10.3390/ijms26031138. 39940906 10.3390/ijms26031138 PMC11818736

42. Irons RD Chen Y Wang X Ryder J Kerzic PJ Acute myeloid leukemia following exposure to benzene more closely resembles de novo than therapy related-disease Genes Chromosomes Cancer 2013 52 887 94 10.1002/gcc.22084 23840003 Irons RD, Chen Y, Wang X, Ryder J, Kerzic PJ. Acute myeloid leukemia following exposure to benzene more closely resembles de novo than therapy related-disease. Genes Chromosomes Cancer. 2013;52:887–94. 10.1002/gcc.22084. 23840003 10.1002/gcc.22084

43. Patel KS Pandey PK Martín-Ramos P Corns WT Varol S Bhattacharya P A review on arsenic in the environment: contamination, mobility, sources, and exposure RSC Adv 2023 13 8803 21 10.1039/D3RA00789H 36936841 PMC10020839 Patel KS, Pandey PK, Martín-Ramos P, Corns WT, Varol S, Bhattacharya P, et al. A review on arsenic in the environment: contamination, mobility, sources, and exposure. RSC Adv. 2023;13:8803–21. 10.1039/D3RA00789H. 36936841 10.1039/d3ra00789h PMC10020839

44. Medina S Zhang H Santos-Medina LV Wan G Bolt AM Zhou X Arsenic impairs the lineage commitment of hematopoietic progenitor cells through the attenuation of GATA-2 DNA binding activity Toxicol Appl Pharmacol 2022 452 116193 10.1016/j.taap.2022.116193 35961411 PMC9583771 Medina S, Zhang H, Santos-Medina LV, Wan G, Bolt AM, Zhou X, et al. Arsenic impairs the lineage commitment of hematopoietic progenitor cells through the attenuation of GATA-2 DNA binding activity. Toxicol Appl Pharmacol. 2022;452:116193. 10.1016/j.taap.2022.116193. 35961411 10.1016/j.taap.2022.116193 PMC9583771

45. Chen QY Costa M PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis Mol Pharmacol 2018 94 784 92 10.1124/mol.118.112268 29769245 PMC5994485 Chen QY, Costa M. PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis. Mol Pharmacol. 2018;94:784–92. 10.1124/mol.118.112268. 29769245 10.1124/mol.118.112268 PMC5994485

46. International Agency for Research on Cancer. 1,3-butadiene, ethylene oxide and vinyl halides (vinyl fluoride, vinyl chloride and vinyl bromide) [Internet]. Available from: https://publications.iarc.who.int/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/1-3-Butadiene-Ethylene-Oxide-And-Vinyl-Halides-Vinyl-Fluoride-Vinyl-Chloride-And-Vinyl-Bromide --2008. Accessed 2026 May 21.

47. Walker VE Fennell TR Upton PB Skopek TR Prevost V Shuker DE Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice Cancer Res 1992 52 4328 34 1643630 Walker VE, Fennell TR, Upton PB, Skopek TR, Prevost V, Shuker DE, et al. Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice. Cancer Res. 1992;52:4328–34. 1643630

48. US Environmental Protection Agency. Basic information about NO2 [Internet]. 2016. Available from: https://www.epa.gov/no2-pollution/basic-information-about-no2 . Accessed 2026 May 21.

49. Han M Guo Z Li G Sang N Nitrogen dioxide inhalation induces genotoxicity in rats Chemosphere 2013 90 2737 42 10.1016/j.chemosphere.2012.11.057 23332788 Han M, Guo Z, Li G, Sang N. Nitrogen dioxide inhalation induces genotoxicity in rats. Chemosphere. 2013;90:2737–42. 10.1016/j.chemosphere.2012.11.057. 23332788 10.1016/j.chemosphere.2012.11.057

50. Mishra A Lelieveld S Pöschl U Berkemeier T Multiphase Kinetic Modeling of Air Pollutant Effects on Protein Modification and Nitrotyrosine Formation in Epithelial Lining Fluid Environ Sci Technol 2023 57 12642 53 10.1021/acs.est.3c03556 37587684 PMC10469477 Mishra A, Lelieveld S, Pöschl U, Berkemeier T. Multiphase Kinetic Modeling of Air Pollutant Effects on Protein Modification and Nitrotyrosine Formation in Epithelial Lining Fluid. Environ Sci Technol. 2023;57:12642–53. 10.1021/acs.est.3c03556. 37587684 10.1021/acs.est.3c03556 PMC10469477

51. Shapiro R Genetic effects of bisulfite (sulfur dioxide) Mutat Res 1977 39 149 75 10.1016/0165-1110(77)90020-3 405577 Shapiro R. Genetic effects of bisulfite (sulfur dioxide). Mutat Res. 1977;39:149–75. 10.1016/0165-1110(77)90020-3. 405577 10.1016/0165-1110(77)90020-3

52. Meng Z Sang N Zhang B Effects of derivatives of sulfur dioxide on micronuclei formation in mouse bone marrow cells in vivo Bull Environ Contam Toxicol 2002 69 257 64 10.1007/s00128-002-0055-0 12107703 Meng Z, Sang N, Zhang B. Effects of derivatives of sulfur dioxide on micronuclei formation in mouse bone marrow cells in vivo. Bull Environ Contam Toxicol. 2002;69:257–64. 10.1007/s00128-002-0055-0. 12107703 10.1007/s00128-002-0055-0

53. Meng Z Qin G Zhang B DNA damage in mice treated with sulfur dioxide by inhalation Environ Mol Mutagen 2005 46 150 5 10.1002/em.20142 15898097 Meng Z, Qin G, Zhang B. DNA damage in mice treated with sulfur dioxide by inhalation. Environ Mol Mutagen. 2005;46:150–5. 10.1002/em.20142. 15898097 10.1002/em.20142

54. Yadav JS Kaushik VK Effect of sulphur dioxide exposure on human chromosomes Mutat Res 1996 359 25 9 10.1016/s0165-1161(96)90006-0 8569799 Yadav JS, Kaushik VK. Effect of sulphur dioxide exposure on human chromosomes. Mutat Res. 1996;359:25–9. 10.1016/s0165-1161(96)90006-0. 8569799 10.1016/s0165-1161(96)90006-0

55. Meng Z Zhang L Cytogenetic damage induced in human lymphocytes by sodium bisulfite Mutat Res 1992 298 63 9 10.1016/0165-1218(92)90030-4 1282213 Meng Z, Zhang L. Cytogenetic damage induced in human lymphocytes by sodium bisulfite. Mutat Res. 1992;298:63–9. 10.1016/0165-1218(92)90030-4. 1282213 10.1016/0165-1218(92)90030-4

56. Leung KH Keller DA Menzel DB Effect of sulfite on the covalent reaction of benzo(a)pyrene metabolites with DNA Carcinogenesis 1989 10 259 64 10.1093/carcin/10.2.259 2912576 Leung KH, Keller DA, Menzel DB. Effect of sulfite on the covalent reaction of benzo(a)pyrene metabolites with DNA. Carcinogenesis. 1989;10:259–64. 10.1093/carcin/10.2.259. 2912576 10.1093/carcin/10.2.259

57. Reed GA Ryan MJ Adams KS Sulfite enhancement of diolepoxide mutagenicity: the role of altered glutathione metabolism Carcinogenesis 1990 11 1635 9 10.1093/carcin/11.9.1635 2119259 Reed GA, Ryan MJ, Adams KS. Sulfite enhancement of diolepoxide mutagenicity: the role of altered glutathione metabolism. Carcinogenesis. 1990;11:1635–9. 10.1093/carcin/11.9.1635. 2119259 10.1093/carcin/11.9.1635

58. Reed GA Curtis JF Mottley C Eling TE Mason RP Epoxidation of (+/-)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene during (bi)sulfite autoxidation: activation of a procarcinogen by a cocarcinogen Proc Natl Acad Sci U S A 1986 83 7499 502 10.1073/pnas.83.19.7499 3463979 PMC386746 Reed GA, Curtis JF, Mottley C, Eling TE, Mason RP. Epoxidation of (+/-)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene during (bi)sulfite autoxidation: activation of a procarcinogen by a cocarcinogen. Proc Natl Acad Sci U S A. 1986;83:7499–502. 10.1073/pnas.83.19.7499. 3463979 10.1073/pnas.83.19.7499 PMC386746

59. Reed GA Sulfite-dependent mutagenicity of benzo[a]pyrene derivatives Carcinogenesis 1987 8 1145 8 10.1093/carcin/8.8.1145 3301047 Reed GA. Sulfite-dependent mutagenicity of benzo[a]pyrene derivatives. Carcinogenesis. 1987;8:1145–8. 10.1093/carcin/8.8.1145. 3301047 10.1093/carcin/8.8.1145

60. Qin G Meng Z Effects of sulfur dioxide derivatives on expression of oncogenes and tumor suppressor genes in human bronchial epithelial cells Food Chem Toxicol 2009 47 734 44 10.1016/j.fct.2009.01.005 19167448 Qin G, Meng Z. Effects of sulfur dioxide derivatives on expression of oncogenes and tumor suppressor genes in human bronchial epithelial cells. Food Chem Toxicol. 2009;47:734–44. 10.1016/j.fct.2009.01.005. 19167448 10.1016/j.fct.2009.01.005

61. Lee WJ Teschke K Kauppinen T Andersen A Jäppinen P Szadkowska-Stanczyk I Mortality from lung cancer in workers exposed to sulfur dioxide in the pulp and paper industry Environ Health Perspect 2002 110 991 5 10.1289/ehp.02110991 12361923 PMC1241024 Lee WJ, Teschke K, Kauppinen T, Andersen A, Jäppinen P, Szadkowska-Stanczyk I, et al. Mortality from lung cancer in workers exposed to sulfur dioxide in the pulp and paper industry. Environ Health Perspect. 2002;110:991–5. 10.1289/ehp.02110991. 12361923 10.1289/ehp.02110991 PMC1241024

62. Infante PF Rinsky RA Wagoner JK Young RJ Leukaemia in benzene workers Lancet 1977 2 76 8 10.1016/s0140-6736(77)90074-5 69157 Infante PF, Rinsky RA, Wagoner JK, Young RJ. Leukaemia in benzene workers. Lancet. 1977;2:76–8. 10.1016/s0140-6736(77)90074-5. 69157 10.1016/s0140-6736(77)90074-5

63. Paustenbach DJ Bass RD Price P Benzene toxicity and risk assessment, 1972–1992: implications for future regulation Environ Health Perspect 1993 101 177 200 10.1289/ehp.93101s6177 8020442 PMC1520014 Paustenbach DJ, Bass RD, Price P. Benzene toxicity and risk assessment, 1972–1992: implications for future regulation. Environ Health Perspect. 1993;101:177–200. 10.1289/ehp.93101s6177. 8020442 10.1289/ehp.93101s6177 PMC1520014

64. Wallace LA Major sources of benzene exposure Environ Health Perspect 1989 82 165 9 10.1289/ehp.8982165 2477239 PMC1568130 Wallace LA. Major sources of benzene exposure. Environ Health Perspect. 1989;82:165–9. 10.1289/ehp.8982165. 2477239 10.1289/ehp.8982165 PMC1568130

65. Wallace L Pellizzari E Hartwell TD Perritt R Ziegenfus R Exposures to benzene and other volatile compounds from active and passive smoking Arch Environ Health 1987 42 272 9 10.1080/00039896.1987.9935820 3452294 Wallace L, Pellizzari E, Hartwell TD, Perritt R, Ziegenfus R. Exposures to benzene and other volatile compounds from active and passive smoking. Arch Environ Health. 1987;42:272–9. 10.1080/00039896.1987.9935820. 3452294 10.1080/00039896.1987.9935820

66. Lan Q Zhang L Li G Vermeulen R Weinberg RS Dosemeci M Hematotoxicity in workers exposed to low levels of benzene Science 2004 306 1774 6 10.1126/science.1102443 15576619 PMC1256034 Lan Q, Zhang L, Li G, Vermeulen R, Weinberg RS, Dosemeci M, et al. Hematotoxicity in workers exposed to low levels of benzene. Science. 2004;306:1774–6. 10.1126/science.1102443. 15576619 10.1126/science.1102443 PMC1256034

67. Johnson GT Harbison SC McCluskey JD Harbison RD Characterization of cancer risk from airborne benzene exposure Regul Toxicol Pharmacol 2009 55 361 6 10.1016/j.yrtph.2009.08.008 19703507 Johnson GT, Harbison SC, McCluskey JD, Harbison RD. Characterization of cancer risk from airborne benzene exposure. Regul Toxicol Pharmacol. 2009;55:361–6. 10.1016/j.yrtph.2009.08.008. 19703507 10.1016/j.yrtph.2009.08.008

68. Glass DC Gray CN Jolley DJ Gibbons C Sim MR Fritschi L Leukemia risk associated with low-level benzene exposure Epidemiology 2003 14 569 77 10.1097/01.ede.0000082001.05563.e0 14501272 Glass DC, Gray CN, Jolley DJ, Gibbons C, Sim MR, Fritschi L, et al. Leukemia risk associated with low-level benzene exposure. Epidemiology. 2003;14:569–77. 10.1097/01.ede.0000082001.05563.e0. 14501272 10.1097/01.ede.0000082001.05563.e0

69. Talbott EO Xu X Youk AO Rager JR Stragand JA Malek AM Risk of leukemia as a result of community exposure to gasoline vapors: a follow-up study Environ Res 2011 111 597 602 10.1016/j.envres.2011.03.009 21453914 Talbott EO, Xu X, Youk AO, Rager JR, Stragand JA, Malek AM. Risk of leukemia as a result of community exposure to gasoline vapors: a follow-up study. Environ Res. 2011;111:597–602. 10.1016/j.envres.2011.03.009. 21453914 10.1016/j.envres.2011.03.009

70. Whitworth KW Symanski E Coker AL Childhood lymphohematopoietic cancer incidence and hazardous air pollutants in Southeast Texas, 1995–2004 Environ Health Perspect 1995 116 1576 80 10.1289/ehp.11593 PMC2592281 19057714 Whitworth KW, Symanski E, Coker AL. Childhood lymphohematopoietic cancer incidence and hazardous air pollutants in Southeast Texas, 1995–2004. Environ Health Perspect. 1995;116:1576–80. 10.1289/ehp.11593. 10.1289/ehp.11593 PMC2592281 19057714

71. Janitz AE Campbell JE Magzamen S Pate A Stoner JA Peck JD Benzene and childhood acute leukemia in Oklahoma Environ Res 2017 158 167 73 10.1016/j.envres.2017.06.015 28645022 PMC5554454 Janitz AE, Campbell JE, Magzamen S, Pate A, Stoner JA, Peck JD. Benzene and childhood acute leukemia in Oklahoma. Environ Res. 2017;158:167–73. 10.1016/j.envres.2017.06.015. 28645022 10.1016/j.envres.2017.06.015 PMC5554454

72. Heck JE Park AS Qiu J Cockburn M Ritz B Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood Int J Hyg Environ Health 2014 217 662 8 10.1016/j.ijheh.2013.12.003 24472648 PMC4071125 Heck JE, Park AS, Qiu J, Cockburn M, Ritz B. Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood. Int J Hyg Environ Health. 2014;217:662–8. 10.1016/j.ijheh.2013.12.003. 24472648 10.1016/j.ijheh.2013.12.003 PMC4071125

73. Carlos-Wallace FM Zhang L Smith MT Rader G Steinmaus C Parental, in utero, and early-life exposure to benzene and the risk of childhood leukemia: a meta-analysis Am J Epidemiol 2016 183 1 14 10.1093/aje/kwv120 26589707 PMC4751231 Carlos-Wallace FM, Zhang L, Smith MT, Rader G, Steinmaus C. Parental, in utero, and early-life exposure to benzene and the risk of childhood leukemia: a meta-analysis. Am J Epidemiol. 2016;183:1–14. 10.1093/aje/kwv120. 26589707 10.1093/aje/kwv120 PMC4751231

74. Filippini T Hatch EE Rothman KJ Heck JE Park AS Crippa A Association between outdoor air pollution and childhood leukemia: a systematic review and dose–response meta-analysis Environ Health Perspect 2019 127 046002 10.1289/EHP4381 31017485 PMC6785230 Filippini T, Hatch EE, Rothman KJ, Heck JE, Park AS, Crippa A, et al. Association between outdoor air pollution and childhood leukemia: a systematic review and dose–response meta-analysis. Environ Health Perspect. 2019;127:046002. 10.1289/EHP4381. 31017485 10.1289/EHP4381 PMC6785230

75. Houot J Marquant F Goujon S Faure L Honoré C Roth M-H Residential Proximity to Heavy-Traffic Roads, Benzene Exposure, and Childhood Leukemia—The GEOCAP Study, 2002–2007 Am J Epidemiol 2015 182 685 93 10.1093/aje/kwv111 26377958 Houot J, Marquant F, Goujon S, Faure L, Honoré C, Roth M-H, et al. Residential Proximity to Heavy-Traffic Roads, Benzene Exposure, and Childhood Leukemia—The GEOCAP Study, 2002–2007. Am J Epidemiol. 2015;182:685–93. 10.1093/aje/kwv111. 26377958 10.1093/aje/kwv111

76. Tamayo-Uria I Boldo E García-Pérez J Gómez-Barroso D Romaguera EP Cirach M Childhood leukaemia risk and residential proximity to busy roads Environ Int 2018 121 332 9 10.1016/j.envint.2018.08.056 30241021 Tamayo-Uria I, Boldo E, García-Pérez J, Gómez-Barroso D, Romaguera EP, Cirach M, et al. Childhood leukaemia risk and residential proximity to busy roads. Environ Int. 2018;121:332–9. 10.1016/j.envint.2018.08.056. 30241021 10.1016/j.envint.2018.08.056

77. Kreis C Héritier H Scheinemann K Hengartner H de Hoogh K Röösli M Childhood cancer and traffic-related air pollution in Switzerland: A nationwide census-based cohort study Environ Int 2022 166 107380 10.1016/j.envint.2022.107380 35809486 Kreis C, Héritier H, Scheinemann K, Hengartner H, de Hoogh K, Röösli M, et al. Childhood cancer and traffic-related air pollution in Switzerland: A nationwide census-based cohort study. Environ Int. 2022;166:107380. 10.1016/j.envint.2022.107380. 35809486 10.1016/j.envint.2022.107380

78. Janitz AE Campbell JE Magzamen S Pate A Stoner JA Peck JD Traffic-related air pollution and childhood acute leukemia in Oklahoma Environ Res 2016 148 102 11 10.1016/j.envres.2016.03.036 27038831 PMC4874884 Janitz AE, Campbell JE, Magzamen S, Pate A, Stoner JA, Peck JD. Traffic-related air pollution and childhood acute leukemia in Oklahoma. Environ Res. 2016;148:102–11. 10.1016/j.envres.2016.03.036. 27038831 10.1016/j.envres.2016.03.036 PMC4874884

79. Ghosh JKC Heck JE Cockburn M Su J Jerrett M Ritz B Prenatal exposure to traffic-related air pollution and risk of early childhood cancers Am J Epidemiol 2013 178 1233 9 10.1093/aje/kwt129 23989198 PMC3792733 Ghosh JKC, Heck JE, Cockburn M, Su J, Jerrett M, Ritz B. Prenatal exposure to traffic-related air pollution and risk of early childhood cancers. Am J Epidemiol. 2013;178:1233–9. 10.1093/aje/kwt129. 23989198 10.1093/aje/kwt129 PMC3792733

80. Sanz Olea E Ojeda Sanchez C Guxens M Cañete A Romaguera EP Gómez-Barroso D Particulate Matter Exposure during Pregnancy and Childhood Leukemia Incidence Atmosphere 2024 15 751 10.3390/atmos15070751 Sanz Olea E, Ojeda Sanchez C, Guxens M, Cañete A, Romaguera EP, Gómez-Barroso D, et al. Particulate Matter Exposure during Pregnancy and Childhood Leukemia Incidence. Atmosphere. 2024;15:751. 10.3390/atmos15070751.

81. Puett RC Poulsen AH Taj T Ketzel M Geels C Brandt J Relationship of leukaemias with long-term ambient air pollution exposures in the adult Danish population Br J Cancer 2020 123 1818 24 10.1038/s41416-020-01058-2 32939055 PMC7722932 Puett RC, Poulsen AH, Taj T, Ketzel M, Geels C, Brandt J, et al. Relationship of leukaemias with long-term ambient air pollution exposures in the adult Danish population. Br J Cancer. 2020;123:1818–24. 10.1038/s41416-020-01058-2. 32939055 10.1038/s41416-020-01058-2 PMC7722932

82. Badaloni C Ranucci A Cesaroni G Zanini G Vienneau D Al-Aidrous F Air pollution and childhood leukaemia: a nationwide case-control study in Italy Occup Environ Med 2013 70 876 83 10.1136/oemed-2013-101604 24142970 Badaloni C, Ranucci A, Cesaroni G, Zanini G, Vienneau D, Al-Aidrous F, et al. Air pollution and childhood leukaemia: a nationwide case-control study in Italy. Occup Environ Med. 2013;70:876–83. 10.1136/oemed-2013-101604. 24142970 10.1136/oemed-2013-101604

83. Otto AA Schraw JM Hoang TT Scheurer ME Abstract B152: county-level particulate matter 2.5 exposure associated with higher rates of pediatric leukemia in Southeast Texas Cancer Epidemiol Biomarkers Prev 2025 34 B152 10.1158/1538-7755.DISP25-B152 Otto AA, Schraw JM, Hoang TT, Scheurer ME. Abstract B152: county-level particulate matter 2.5 exposure associated with higher rates of pediatric leukemia in Southeast Texas. Cancer Epidemiol Biomarkers Prev. 2025;34:B152. 10.1158/1538-7755.DISP25-B152.

84. Calderon-Hernandez J Jarquin-Yañez L Reyes-Arreguin L Diaz-Padilla LA Gonzalez-Compean JL Gonzalez-Montalvo P Childhood acute lymphoblastic leukemia survival and spatial analysis of socio-environmental risks in Mexico Front Oncol 2023 13 1236942 10.3389/fonc.2023.1236942 37901312 PMC10603203 Calderon-Hernandez J, Jarquin-Yañez L, Reyes-Arreguin L, Diaz-Padilla LA, Gonzalez-Compean JL, Gonzalez-Montalvo P, et al. Childhood acute lymphoblastic leukemia survival and spatial analysis of socio-environmental risks in Mexico. Front Oncol. 2023;13:1236942. 10.3389/fonc.2023.1236942. 37901312 10.3389/fonc.2023.1236942 PMC10603203

85. Symanski E Tee Lewis PG Chen T-Y Chan W Lai D Ma X Air toxics and early childhood acute lymphocytic leukemia in Texas, a population based case control study Environ Health 2016 15 1 70 10.1186/s12940-016-0154-8 27301866 PMC4908700 Symanski E, Tee Lewis PG, Chen T-Y, Chan W, Lai D, Ma X. Air toxics and early childhood acute lymphocytic leukemia in Texas, a population based case control study. Environ Health. 2016;15:70. 10.1186/s12940-016-0154-8. 27301866 10.1186/s12940-016-0154-8 PMC4908700

86. Yen H-C Chen I-C Lin W-S Lin K-C Wu M-C Lin C-H Prenatal exposure to air pollution and pediatric acute leukemia: a nationwide study Sci Total Environ 2025 992 179975 10.1016/j.scitotenv.2025.179975 40570394 Yen H-C, Chen I-C, Lin W-S, Lin K-C, Wu M-C, Lin C-H. Prenatal exposure to air pollution and pediatric acute leukemia: a nationwide study. Sci Total Environ. 2025;992:179975. 10.1016/j.scitotenv.2025.179975. 40570394 10.1016/j.scitotenv.2025.179975

87. Taj T Poulsen AH Ketzel M Geels C Brandt J Christensen JH Long-term exposure to PM2.5 and its constituents and risk of Non-Hodgkin lymphoma in Denmark: a population-based case–control study Environ Res 2020 188 109762 10.1016/j.envres.2020.109762 32535359 Taj T, Poulsen AH, Ketzel M, Geels C, Brandt J, Christensen JH, et al. Long-term exposure to PM2.5 and its constituents and risk of Non-Hodgkin lymphoma in Denmark: a population-based case–control study. Environ Res. 2020;188:109762. 10.1016/j.envres.2020.109762. 32535359 10.1016/j.envres.2020.109762

88. Parodi S Santi I Marani E Casella C Puppo A Vercelli M Risk of Non-Hodgkin’s Lymphoma and Residential Exposure to Air Pollution in an Industrial Area in Northern Italy: A Case-Control Study Arch Environ Occup Health 2014 69 139 47 10.1080/19338244.2013.763756 24325744 Parodi S, Santi I, Marani E, Casella C, Puppo A, Vercelli M, et al. Risk of Non-Hodgkin’s Lymphoma and Residential Exposure to Air Pollution in an Industrial Area in Northern Italy: A Case-Control Study. Arch Environ Occup Health. 2014;69:139–47. 10.1080/19338244.2013.763756. 24325744 10.1080/19338244.2013.763756

89. Raaschou-Nielsen O Hertel O Thomsen BL Olsen JH Air pollution from traffic at the residence of children with cancer Am J Epidemiol 2001 153 433 43 10.1093/aje/153.5.433 11226975 Raaschou-Nielsen O, Hertel O, Thomsen BL, Olsen JH. Air pollution from traffic at the residence of children with cancer. Am J Epidemiol. 2001;153:433–43. 10.1093/aje/153.5.433. 11226975 10.1093/aje/153.5.433

90. Ramis R Vidal E García-Pérez J Lope V Aragonés N Pérez-Gómez B Study of non-Hodgkin’s lymphoma mortality associated with industrial pollution in Spain, using Poisson models BMC Public Health 2009 9 26 10.1186/1471-2458-9-26 19159450 PMC2662834 Ramis R, Vidal E, García-Pérez J, Lope V, Aragonés N, Pérez-Gómez B, et al. Study of non-Hodgkin’s lymphoma mortality associated with industrial pollution in Spain, using Poisson models. BMC Public Health. 2009;9:26. 10.1186/1471-2458-9-26. 19159450 10.1186/1471-2458-9-26 PMC2662834

91. Viel J-F Daniau C Goria S Fabre P De Crouy-Chanel P Sauleau E-A Risk for non Hodgkin’s lymphoma in the vicinity of French municipal solid waste incinerators Environ Health 2008 7 51 10.1186/1476-069X-7-51 18959776 PMC2587460 Viel J-F, Daniau C, Goria S, Fabre P, De Crouy-Chanel P, Sauleau E-A, et al. Risk for non Hodgkin’s lymphoma in the vicinity of French municipal solid waste incinerators. Environ Health. 2008;7:51. 10.1186/1476-069X-7-51. 18959776 10.1186/1476-069X-7-51 PMC2587460

92. Gaspard E Frenoy P Praud D Coudon T Grassot L Mancini F Association between Cumulative Airborne Dioxin Exposure and Chronic Lymphocytic Leukemia/Non-Hodgkin’s Lymphoma Risk in a Nested Case-Control Study within the French E3N Cohort Blood 2022 140 7036 7 10.1182/blood-2022-166873 37778544 Gaspard E, Frenoy P, Praud D, Coudon T, Grassot L, Mancini F, et al. Association between Cumulative Airborne Dioxin Exposure and Chronic Lymphocytic Leukemia/Non-Hodgkin’s Lymphoma Risk in a Nested Case-Control Study within the French E3N Cohort. Blood. 2022;140:7036–7. 10.1182/blood-2022-166873. 10.1016/j.scitotenv.2023.167330 37778544

93. Nisse C Haguenoer JM Grandbastien B Preudhomme C Fontaine B Brillet JM Occupational and environmental risk factors of the myelodysplastic syndromes in the North of France Br J Haematol 2001 112 927 35 10.1046/j.1365-2141.2001.02645.x 11298587 Nisse C, Haguenoer JM, Grandbastien B, Preudhomme C, Fontaine B, Brillet JM, et al. Occupational and environmental risk factors of the myelodysplastic syndromes in the North of France. Br J Haematol. 2001;112:927–35. 10.1046/j.1365-2141.2001.02645.x. 11298587 10.1046/j.1365-2141.2001.02645.x

94. Schnatter AR Glass DC Tang G Irons RD Rushton L Myelodysplastic Syndrome and Benzene Exposure Among Petroleum Workers: An International Pooled Analysis J Natl Cancer Inst 2012 104 1724 37 10.1093/jnci/djs411 23111193 PMC3502195 Schnatter AR, Glass DC, Tang G, Irons RD, Rushton L. Myelodysplastic Syndrome and Benzene Exposure Among Petroleum Workers: An International Pooled Analysis. J Natl Cancer Inst. 2012;104:1724–37. 10.1093/jnci/djs411. 23111193 10.1093/jnci/djs411 PMC3502195

95. Stafford D White A West R 114 Cytogenetic abnormalities in the myelodysplastic syndromes and occupational or environmental exposure Leuk Res 1997 21 S30 10.1016/S0145-2126(97)81329-X 10706879 Stafford D, White A, West R. 114 Cytogenetic abnormalities in the myelodysplastic syndromes and occupational or environmental exposure. Leuk Res. 1997;21:S30. 10.1016/S0145-2126(97)81329-X. 10706879

96. Abohashem S Aldosoky W Uddin MM Civieri G Lau HC AbiKaram K Abstract 4144992: ambient air pollution heightens prevalence and adverse impacts of clonal hematopoiesis of indeterminate potential Circulation 2024 150 Suppl 1 4144992 10.1161/circ.150.suppl_1.4144992 Abohashem S, Aldosoky W, Uddin MM, Civieri G, Lau HC, AbiKaram K, et al. Abstract 4144992: ambient air pollution heightens prevalence and adverse impacts of clonal hematopoiesis of indeterminate potential. Circulation. 2024;150(Suppl 1):4144992. 10.1161/circ.150.suppl_1.4144992.

97. Jasra S Giricz O Zeig-Owens R Pradhan K Goldfarb DG Barreto-Galvez A High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster Nat Med 2022 28 468 71 10.1038/s41591-022-01708-3 35256801 PMC9394171 Jasra S, Giricz O, Zeig-Owens R, Pradhan K, Goldfarb DG, Barreto-Galvez A, et al. High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster. Nat Med. 2022;28:468–71. 10.1038/s41591-022-01708-3. 35256801 10.1038/s41591-022-01708-3 PMC9394171

98. Leiser CL, Whitsel EA, Reiner A, Quraishi SM, Rich S, Rotter J et al. Associations between ambient air pollutants and clonal hematopoiesis of indeterminate potential (CHIP). ISEE Conf Abstr. 2021;2021:isee.2021.P-535. 10.1289/isee.2021.P-535 10.1158/1055-9965.EPI-23-0305 PMC10592307 37466697

99. Vigliani EC Leukemia associated with benzene exposure Ann N Y Acad Sci 1976 271 143 51 10.1111/j.1749-6632.1976.tb23103.x 1069497 Vigliani EC. Leukemia associated with benzene exposure. Ann N Y Acad Sci. 1976;271:143–51. 10.1111/j.1749-6632.1976.tb23103.x. 1069497 10.1111/j.1749-6632.1976.tb23103.x

100. Rushton L Romaniuk H A case-control study to investigate the risk of leukaemia associated with exposure to benzene in petroleum marketing and distribution workers in the United Kingdom Occup Environ Med 1997 54 152 66 10.1136/oem.54.3.152 9155776 PMC1128678 Rushton L, Romaniuk H. A case-control study to investigate the risk of leukaemia associated with exposure to benzene in petroleum marketing and distribution workers in the United Kingdom. Occup Environ Med. 1997;54:152–66. 10.1136/oem.54.3.152. 9155776 10.1136/oem.54.3.152 PMC1128678

101. Sielken RL Valdez-Flores C A comprehensive review of occupational and general population cancer risk: 1,3-Butadiene exposure–response modeling for all leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, myeloid neoplasm and lymphoid neoplasm Chem Biol Interact 2015 241 50 8 10.1016/j.cbi.2015.06.009 26070419 Sielken RL, Valdez-Flores C. A comprehensive review of occupational and general population cancer risk: 1,3-Butadiene exposure–response modeling for all leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, myeloid neoplasm and lymphoid neoplasm. Chem Biol Interact. 2015;241:50–8. 10.1016/j.cbi.2015.06.009. 26070419 10.1016/j.cbi.2015.06.009

102. Vlaanderen J Lan Q Kromhout H Rothman N Vermeulen R Occupational benzene exposure and the risk of chronic myeloid leukemia: a meta-analysis of cohort studies incorporating study quality dimensions Am J Ind Med 2012 55 779 85 10.1002/ajim.22087 22729623 Vlaanderen J, Lan Q, Kromhout H, Rothman N, Vermeulen R. Occupational benzene exposure and the risk of chronic myeloid leukemia: a meta-analysis of cohort studies incorporating study quality dimensions. Am J Ind Med. 2012;55:779–85. 10.1002/ajim.22087. 22729623 10.1002/ajim.22087

103. Hvidtfeldt UA Chen J Rodopoulou S Strak M De Hoogh K Andersen ZJ Multiple myeloma risk in relation to long-term air pollution exposure - a pooled analysis of four European cohorts Environ Res 2023 239 117230 10.1016/j.envres.2023.117230 37806476 Hvidtfeldt UA, Chen J, Rodopoulou S, Strak M, De Hoogh K, Andersen ZJ, et al. Multiple myeloma risk in relation to long-term air pollution exposure - a pooled analysis of four European cohorts. Environ Res. 2023;239:117230. 10.1016/j.envres.2023.117230. 37806476 10.1016/j.envres.2023.117230

104. Wysota M Pradhan K Jacobs S Rosiene J Hall C Downward G Fine particulate matter exposure is linked to worse myeloma outcomes in a diverse urban cohort Blood Cancer J 2025 15 115 10.1038/s41408-025-01301-0 40619445 PMC12230138 Wysota M, Pradhan K, Jacobs S, Rosiene J, Hall C, Downward G, et al. Fine particulate matter exposure is linked to worse myeloma outcomes in a diverse urban cohort. Blood Cancer J. 2025;15:115. 10.1038/s41408-025-01301-0. 40619445 10.1038/s41408-025-01301-0 PMC12230138

105. Morris PD Koepsell TD Daling JR Taylor JW Lyon JL Swanson GM Toxic substance exposure and multiple myeloma: a case-control study J Natl Cancer Inst 1986 76 987 94 3458965 Morris PD, Koepsell TD, Daling JR, Taylor JW, Lyon JL, Swanson GM, et al. Toxic substance exposure and multiple myeloma: a case-control study. J Natl Cancer Inst. 1986;76:987–94. 3458965

106. Wong O Is There a Causal Relationship Between Exposure to Diesel Exhaust and Multiple Myeloma? Toxicol Rev 2003 22 91 102 10.2165/00139709-200322020-00004 15071819 Wong O. Is There a Causal Relationship Between Exposure to Diesel Exhaust and Multiple Myeloma? Toxicol Rev. 2003;22:91–102. 10.2165/00139709-200322020-00004. 15071819 10.2165/00139709-200322020-00004

107. Colmer J Hardman I Shimshack J Voorheis J Disparities in PM2.5 air pollution in the United States Science 2020 369 575 8 10.1126/science.aaz9353 32732425 Colmer J, Hardman I, Shimshack J, Voorheis J. Disparities in PM2.5 air pollution in the United States. Science. 2020;369:575–8. 10.1126/science.aaz9353. 32732425 10.1126/science.aaz9353

108. Zou B Peng F Wan N Mamady K Wilson GJ Spatial cluster detection of air pollution exposure inequities across the United States PLoS One 2014 9 e91917 10.1371/journal.pone.0091917 24647354 PMC3960143 Zou B, Peng F, Wan N, Mamady K, Wilson GJ. Spatial cluster detection of air pollution exposure inequities across the United States. PLoS One. 2014;9:e91917. 10.1371/journal.pone.0091917. 24647354 10.1371/journal.pone.0091917 PMC3960143

109. Ringquist EJ Assessing evidence of environmental inequities: A meta-analysis J Policy Anal Manag 2005 24 223 47 10.1002/pam.20088 Ringquist EJ. Assessing evidence of environmental inequities: A meta-analysis. J Policy Anal Manag. 2005;24:223–47. 10.1002/pam.20088.

110. Jbaily A Zhou X Liu J Lee T-H Kamareddine L Verguet S Air pollution exposure disparities across US population and income groups Nature 2022 601 228 33 10.1038/s41586-021-04190-y 35022594 PMC10516300 Jbaily A, Zhou X, Liu J, Lee T-H, Kamareddine L, Verguet S, et al. Air pollution exposure disparities across US population and income groups. Nature. 2022;601:228–33. 10.1038/s41586-021-04190-y. 35022594 10.1038/s41586-021-04190-y PMC10516300

111. Zhang J Day D Nadadur SS Hollingsworth JW Urban air pollution and health in developing countries Air pollution and health effects 2015 London Springer 355 80 Zhang J, Day D. Urban air pollution and health in developing countries. In: Nadadur SS, Hollingsworth JW, editors. Air pollution and health effects. London: Springer; 2015. p. 355–80. 10.1007/978-1-4471-6669-6_13.

112. McGranahan G Murray F Air pollution and health in rapidly developing countries 2012 London Routledge McGranahan G, Murray F, editors. Air pollution and health in rapidly developing countries. London: Routledge; 2012. 10.4324/9781849770460.

113. Yabroff KR Mariotto A Tangka F Zhao J Islami F Sung H Annual report to the nation on the status of cancer, part 2: patient economic burden associated with cancer care J Natl Cancer Inst 2021 113 1670 82 10.1093/jnci/djab192 34698839 PMC9891103 Yabroff KR, Mariotto A, Tangka F, Zhao J, Islami F, Sung H, et al. Annual report to the nation on the status of cancer, part 2: patient economic burden associated with cancer care. J Natl Cancer Inst. 2021;113:1670–82. 10.1093/jnci/djab192. 34698839 10.1093/jnci/djab192 PMC9891103

114. Cusatis R Tan I Piehowski C Akinola I Crawford E Craig J Worsening Financial Toxicity Among Patients Receiving Chimeric Antigen Receptor t-Cell (CAR-T) Therapy: A Mixed Methods Longitudinal Study Blood 2021 138 567 10.1182/blood-2021-146032 Cusatis R, Tan I, Piehowski C, Akinola I, Crawford E, Craig J, et al. Worsening Financial Toxicity Among Patients Receiving Chimeric Antigen Receptor t-Cell (CAR-T) Therapy: A Mixed Methods Longitudinal Study. Blood. 2021;138:567. 10.1182/blood-2021-146032.

115. Maziarz RT Gergis U Edwards ML Song Y Liu Q Anderson A Health care costs among patients with hematologic malignancies receiving allogeneic transplants: a US payer perspective Blood Adv 2024 8 1200 8 10.1182/bloodadvances.2023011033 38055922 PMC10912849 Maziarz RT, Gergis U, Edwards ML, Song Y, Liu Q, Anderson A, et al. Health care costs among patients with hematologic malignancies receiving allogeneic transplants: a US payer perspective. Blood Adv. 2024;8:1200–8. 10.1182/bloodadvances.2023011033. 38055922 10.1182/bloodadvances.2023011033 PMC10912849

116. Abel GA Albelda R Khera N Hahn T Salas Coronado DY Odejide OO Financial Hardship and Patient-Reported Outcomes after Hematopoietic Cell Transplantation Biol Blood Marrow Transpl 2016 22 1504 10 10.1016/j.bbmt.2016.05.008 PMC4949125 27184627 Abel GA, Albelda R, Khera N, Hahn T, Salas Coronado DY, Odejide OO, et al. Financial Hardship and Patient-Reported Outcomes after Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2016;22:1504–10. 10.1016/j.bbmt.2016.05.008. 10.1016/j.bbmt.2016.05.008 PMC4949125 27184627

117. Denzen EM Thao V Hahn T Lee SJ McCarthy PL Rizzo JD Financial Impact of Allogeneic Hematopoietic Cell Transplantation on Patients and Families over 2-years: Results from a Multicenter Pilot Study Bone Marrow Transpl 2016 51 1233 40 10.1038/bmt.2016.103 PMC5014617 27088381 Denzen EM, Thao V, Hahn T, Lee SJ, McCarthy PL, Rizzo JD, et al. Financial Impact of Allogeneic Hematopoietic Cell Transplantation on Patients and Families over 2-years: Results from a Multicenter Pilot Study. Bone Marrow Transpl. 2016;51:1233–40. 10.1038/bmt.2016.103. 10.1038/bmt.2016.103 PMC5014617 27088381

118. Zafar SY Peppercorn JM Schrag D Taylor DH Goetzinger AM Zhong X The financial toxicity of cancer treatment: a pilot study assessing out-of‐pocket expenses and the insured cancer patient’s experience Oncologist 2013 18 381 90 10.1634/theoncologist.2012-0279 23442307 PMC3639525 Zafar SY, Peppercorn JM, Schrag D, Taylor DH, Goetzinger AM, Zhong X, et al. The financial toxicity of cancer treatment: a pilot study assessing out-of‐pocket expenses and the insured cancer patient’s experience. Oncologist. 2013;18:381–90. 10.1634/theoncologist.2012-0279. 23442307 10.1634/theoncologist.2012-0279 PMC3639525

119. Longo CJ Fitch MI Loree JM Carlson LE Turner D Cheung WY Patient and family financial burden associated with cancer treatment in Canada: a national study Support Care Cancer 2021 29 3377 86 10.1007/s00520-020-05907-x 33403399 PMC8062343 Longo CJ, Fitch MI, Loree JM, Carlson LE, Turner D, Cheung WY, et al. Patient and family financial burden associated with cancer treatment in Canada: a national study. Support Care Cancer. 2021;29:3377–86. 10.1007/s00520-020-05907-x. 33403399 10.1007/s00520-020-05907-x PMC8062343

120. Moran JR Short PF Hollenbeak CS Long-Term Employment Effects of Surviving Cancer J Health Econ 2011 30 505 14 10.1016/j.jhealeco.2011.02.001 21429606 PMC3110504 Moran JR, Short PF, Hollenbeak CS. Long-Term Employment Effects of Surviving Cancer. J Health Econ. 2011;30:505–14. 10.1016/j.jhealeco.2011.02.001. 21429606 10.1016/j.jhealeco.2011.02.001 PMC3110504

121. Parker C Liew D Ademi Z Owen AJ Ayton D Wei A Estimating the Productivity Impact of Acute Myeloid Leukemia in Australia Between 2020 and 2029, Using a Novel Work Utility Measure: The Productivity-Adjusted Life Year (PALY) JCO Oncol Pract 2021 17 e1803 10 10.1200/OP.20.00904 33979179 Parker C, Liew D, Ademi Z, Owen AJ, Ayton D, Wei A, et al. Estimating the Productivity Impact of Acute Myeloid Leukemia in Australia Between 2020 and 2029, Using a Novel Work Utility Measure: The Productivity-Adjusted Life Year (PALY). JCO Oncol Pract. 2021;17:e1803–10. 10.1200/OP.20.00904. 33979179 10.1200/OP.20.00904

122. Dieguez G, Ferro C, Pyenson B. A multi-year look at the cost burden of cancer care [Internet]. Milliman; 2017. Available from: https://www.milliman.com/en/insight/2017/a-multi-year-look-at-the-cost-burden-of-cancer-care . Accessed 2026 May 21.

123. Spellman SR Xu K Oloyede T Ahn KW Akhtar O Bolon Y-T Current Activity Trends and Outcomes in Hematopoietic Cell Transplantation and Cellular Therapy - A Report from the CIBMTR Transpl Cell Ther 2025 31 505 32 10.1016/j.jtct.2025.05.014 PMC12302970 40398621 Spellman SR, Xu K, Oloyede T, Ahn KW, Akhtar O, Bolon Y-T, et al. Current Activity Trends and Outcomes in Hematopoietic Cell Transplantation and Cellular Therapy - A Report from the CIBMTR. Transpl Cell Ther. 2025;31:505–32. 10.1016/j.jtct.2025.05.014. 10.1016/j.jtct.2025.05.014 PMC12302970 40398621

124. Heine R Thielen FW Koopmanschap M Kersten MJ Einsele H Jaeger U Health Economic Aspects of Chimeric Antigen Receptor T-cell Therapies for Hematological Cancers: Present and Future HemaSphere 2021 5 e524 10.1097/HS9.0000000000000524 33880433 PMC8051992 Heine R, Thielen FW, Koopmanschap M, Kersten MJ, Einsele H, Jaeger U, et al. Health Economic Aspects of Chimeric Antigen Receptor T-cell Therapies for Hematological Cancers: Present and Future. HemaSphere. 2021;5:e524. 10.1097/HS9.0000000000000524. 33880433 10.1097/HS9.0000000000000524 PMC8051992

125. US Environmental Protection Agency. Air quality dispersion modeling - alternative models [Internet]. 2016. Available from: https://www.epa.gov/scram/air-quality-dispersion-modeling-alternative-models . Accessed 2026 May 21.

126. Goldstein BD Liu Y Wu F Lioy P Comparison of the effects of the US Clean Air Act and of smoking prevention and cessation efforts on the risk of acute myelogenous leukemia Am J Public Health 2011 101 2357 61 10.2105/AJPH.2011.300256 22021318 PMC3222429 Goldstein BD, Liu Y, Wu F, Lioy P. Comparison of the effects of the US Clean Air Act and of smoking prevention and cessation efforts on the risk of acute myelogenous leukemia. Am J Public Health. 2011;101:2357–61. 10.2105/AJPH.2011.300256. 22021318 10.2105/AJPH.2011.300256 PMC3222429