Outdoor air pollution (OAP) is a global environmental health threat long associated with respiratory disease and solid tumors. This review synthesizes available molecular and epidemiologic evidence that links OAP exposure to a spectrum of hematologic malignancies, including acute and chronic leukemias, lymphomas, myelodysplastic syndromes (MDS), clonal hematopoiesis of indeterminate potential (CHIP), and multiple myeloma (MM). The authors emphasize both mechanistic pathways and population-level studies to assess plausibility and epidemiologic strength.
The review identifies a set of pollutants most frequently implicated in hematologic carcinogenesis: particulate matter (PM), benzene, nitrogen dioxide (NO₂), sulfur dioxide (SO₂), arsenic, and ethylene oxide. These agents vary in source, physicochemical properties, and capacity to reach and affect the bone marrow and circulating hematopoietic cells. Benzene and PM are highlighted repeatedly in the literature as having biologic and epidemiologic links to hematologic disease.
Proposed molecular mechanisms that connect OAP exposure to hematologic neoplasia include:
Oxidative stress leading to reactive oxygen species and cellular injury.
Direct and indirect DNA damage that can produce mutations relevant to leukemogenesis and lymphomagenesis.
Epigenetic dysregulation altering gene expression patterns without changing DNA sequence.
Chronic inflammation creating a microenvironment that can support malignant transformation.
Hematopoietic stem cell dysfunction, which may predispose to clonal expansion and progression to overt malignancy.
These mechanisms provide biological plausibility for epidemiologic associations but do not, on their own, establish causality in humans.
Epidemiologic evidence is described as strongest for acute myeloid leukemia (AML), particularly in relation to benzene exposure. Studies summarized in the review support a link between benzene and AML risk, consistent with known occupational and environmental benzene toxicity.
For acute lymphoblastic leukemia (ALL), associations have been reported with traffic-related pollution, NO₂, and PM, but findings are less consistent across studies than for AML. The review notes heterogeneity in study results and exposure assessment methods, which complicates interpretation.
Certain lymphoma subtypes show pollutant-specific associations in the epidemiologic literature. The review indicates that links vary by lymphoma subtype and pollutant, with some evidence pointing toward relationships with specific air pollutants. However, subtype heterogeneity and differing exposure metrics across studies limit definitive conclusions.
The authors report emerging links between OAP exposure and myelodysplastic syndromes (MDS) and clonal hematopoiesis of indeterminate potential (CHIP). Evidence in these areas is newer and less extensive than for acute leukemias, but mechanistic pathways such as stem cell damage and mutagenesis could plausibly connect exposure to clonal hematopoietic changes and progression toward overt myeloid neoplasia.
In contrast to AML, ALL, and some lymphoma subtypes, the review states that evidence linking OAP to chronic leukemias and multiple myeloma (MM) remains limited. Fewer studies are available, and the existing epidemiologic data do not yet establish robust associations for these disease categories.
The authors underscore important methodological limitations across the literature, notably exposure misclassification and residual confounding, which weaken causal inference. Variability in pollutant measurement, temporal and spatial exposure assessment, and differing study designs contribute to inconsistent findings.
The review also highlights environmental justice concerns: OAP exposure disproportionately affects racial and ethnic minorities, low-income communities, and populations in rapidly industrializing regions, amplifying existing health disparities related to cancer risk and outcomes.
Cumulative molecular and epidemiologic evidence summarized in the review supports the characterization of OAP as an important and potentially modifiable risk factor for several hematologic malignancies. The authors call for further research to address exposure assessment limitations, clarify disease- and subtype-specific risks, and elucidate mechanistic pathways linking pollutants to hematopoietic carcinogenesis.
They also advocate for environmental policy reform and public health interventions to reduce OAP exposure—actions that could mitigate disease burden and lessen disparities in affected communities.
Taken together, mechanistic data and epidemiologic studies provide convergent evidence that certain air pollutants, including PM and benzene, are plausibly linked to hematologic malignancies, with the strongest epidemiologic signal for AML. Evidence for ALL, selected lymphoma subtypes, MDS, and CHIP is growing, while data for chronic leukemias and MM are limited. Despite study limitations such as exposure misclassification and residual confounding, the review concludes that OAP represents a potentially modifiable environmental risk factor and urges additional research, policy action, and targeted public health measures to reduce exposures and health inequities.