Breath of Danger: Unveiling PM2.5’s Stealthy Impact on Cancer Risks

Exposure to PM2.5 and Cancer Risk

PM2.5 has been implicated in the etiology of pulmonary disease, diabetes mellitus, cardiovascular disease, adverse birth outcomes, and cancer (3, 4). Oxidative stress and inflammation emerge as key mechanisms explaining PM-associated cancer mortality. PM induces oxidative stress in epithelial cells, generating reactive oxygen species that may damage DNA, proteins, and lipids (6). Furthermore, inflammation, triggered by PM2.5 stimulates the production of chemokines and cytokines, promoting angiogenesis. This process facilitates the invasion of epithelial cells by metastatic tumor cells, contributing to the survival of malignant cells in distant organs. The carcinogenic risk associated with PM2.5 extends beyond the respiratory system, potentially affecting other organs (7).

In terms of the digestive tract, PM2.5 exposure is linked to cancer through inflammation of gut lining epithelial cells, alterations in immune responses, and impacts on gut microbiota (8). These effects may be related to aerosolized pollutants trapped by mucus, affecting the epithelial lining and microbiota of the digestive tract.

Wong et al. reported that long-term exposure to PM2.5 was associated with an elevated risk of mortality across all cancer types [hazard ratio (HR)=1.22, 95% confidence interval (CI)=1.11-1.34]. Specific increases were observed in cancers of the upper digestive tract [1.42 (1.06-1.89)] and digestive accessory organs [1.35 (1.06-1.71)] for all subjects. In females, breast cancer risk rose to [1.80 (1.26-2.55)], while in males, lung cancer risk increased to [1.36 (1.05-1.77)] (9). Furthermore, PM2.5 has been associated with an increased risk of lung, bladder and colorectal cancer (2).

The relationship between cancer risk and PM2.5 appears to be linear. For every 10 μg/m3 increase in the three-year-average concentrations of PM2.5 (current year and previous two years), the relative risks (RR) of cancer mortality were 1.16 (95%CI=1.11-1.20) for all-site cancers, with even low levels having a significant impact on cancer mortality risk (10).

In addition to the genotoxic effects of PM2.5, attached PAHs are recognized to be endocrine disrupting chemicals (EDCs) with specific implications for breast and prostate cancer (11).

PM2.5 Exposure and Breast Cancer Risk

Exposure to any level of PAHs was linked to a higher risk of breast cancer [odds ratio (OR)=1.32, 95%CI=1.10-1.59]. Additionally, extended exposure duration (>7.4 years) to high PAH levels was associated with an increased risk (OR=1.45, 95%CI=1.10-1.91; p for trend=0.01) compared to women who were never exposed (12).

The NIH All of Us Research Program, encompassing 544,000 participants nationwide, recently disclosed a noteworthy link between PM2.5 and breast, ovarian, and endometrial cancers (13). A pooled analysis of six European cohorts indicated a positive correlation between ambient PM2.5 exposure and breast cancer, with a HR of 1.06 (1.01-1.11) per 5 μg/m³ (14). Moreover, a meta-analysis demonstrated a 1.17-fold risk increase in breast cancer mortality for every 10 μg/m³ rise in PM2.5 (15). Hence long-term exposure to PM2.5 pollution not only raises the risk of breast cancer but also seems linked to a more aggressive disease and a poorer prognosis.

Emerging evidence highlights genetic predisposition’s role in the interplay between air pollution and cancer risk, with genetically predicted PM2.5 exposure being associated with higher risks of ER+ (OR=1.24, 95%CI=1.03-1.5, p=0.02) and ER− (OR=2.57, 95%CI=1.05-6.3, p=0.04) breast cancer (16).

We previously reported a positive association between residence in urban areas and high mammographic density, a known predictor of future breast cancer risk (17). Our observations were partly attributed to elevated levels of air pollution associated with urbanization, including traffic emissions.

PM2.5 Exposure and Prostate Cancer Risk

In a recent cohort study involving millions of Medicare beneficiaries across the contiguous US, clear evidence emerged, indicating that chronic exposures to PM2.5 heightened the risk of prostate cancers within a 10-year period leading up to diagnosis. The heightened risk persists regardless of exposure levels, with a single unit reduction in long-term PM2.5 potentially preventing at least 460 annual cases in the cohort (18). This aligns with other epidemiological findings. In a population-based Canadian case-control study, significant correlations between exposure to PM2.5 over the past two decades and prostate cancer were observed (19). An interquartile range (IQR) increase in PM2.5 (3.56 μg/m³ for satellite and 4.48 μg/m³ for scaled satellite observations) resulted in ORs of 1.28 (95%CI=1.07-1.52) and 1.20 (95%CI=1.03-1.40), respectively resulting in a 20-28% relative increase in prostate cancer risk.

Mitigation of PM2.5 Adverse Effects

Subjects exposed to elevated ambient PM2.5 levels should consider mitigating oxidative stress by increasing antioxidant intake through diet and/or supplements. Carotenoids like alpha and beta carotene, as well as lycopene, may provide protection against gastrointestinal, prostate, and breast cancer (20). Additionally, polyphenols, such as flavonoids found in green tea, vegetables, and fruits, seem to lower the risk of various cancers, including lung, breast, prostate, and gastrointestinal tumors (16). Other compounds like curcumin, vitamin B6, folate, vitamin D, quercetin, sulforaphane, insole-3-carbinol, vitamin C, vitamin E, and Omega-3 polyunsaturated fatty acids have also demonstrated chemo-preventative effects against human cancer (21, 22). Hence, adopting a Mediterranean diet that includes fish, legumes, fresh fruits, and vegetables like berries, kale, broccoli, and tomatoes, along with vitamin D3 supplements, is recommended in high air pollution environments. Administering antioxidants through inhalation (pulmonary or nasal) offers a promising approach, potentially elevating antioxidant levels in the airway surface liquid to safeguard against oxidative damage caused by air pollution. These compounds are currently being investigated (22).

Policy makers should enact measures to reduce PM 2.5 emissions, including promoting clean energy, gradual phasing out of fossil fuels, prohibiting oil industry flaring which is a significant source of PM2.5 in oil producing countries (23), encouraging the adoption of electric vehicles and public transportation, implementing urban planning strategies, and regulating industrial emissions. However, it is important to note that commercially available face masks exhibit limited efficacy in shielding individuals from exposure, primarily attributed to their sub-optimal filtering capacity and ill-fitting nature (24).

While mechanical air ventilation with efficient filters plays a role in maintaining indoor air quality in residential houses, it’s important to acknowledge its limitations and explore complementary strategies to address potential gaps in minimizing exposure to fine particulate matter (25). Engaging in effective cancer screening programs, particularly for breast, lung, colorectal, prostate and cervical cancer, becomes increasingly crucial for individuals residing in regions characterized by elevated air pollution levels.

Challenges and Future Research

Despite the progress made in understanding the health risks associated with PM2.5, several challenges and avenues for future research exist. The variability of PM2.5 composition across different regions and sources warrants further investigation to tailor mitigation strategies to specific environmental contexts. The underlying mechanisms and potential contributing genetic factors mediating cancer risk, require further research.

Collaborative efforts between scientists, healthcare professionals, and policymakers are essential to formulate comprehensive strategies that protect public health and mitigate the impact of PM2.5 on cancer risks.

Air pollution awareness programs should emphasize the impact of human activities such as smoking and cooking on both indoor and outdoor air quality. The rising prevalence of vaping is emerging as a notable source of PM2.5 air pollution (26).

Recent evidence indicates that heightened environmental regulation substantially diminishes health risks in urban areas. A one-unit escalation in the level of environmental regulation correlates with a roughly 15.4% reduction in the overall count of premature deaths attributed to stroke, ischemic heart disease, and lung cancer. This conclusion withstands scrutiny through various robustness tests (27).