Micro/nanoplastics and cancer: Focus on gastrointestinal malignancies
image: MNPs in modern ecosystems have become a pressing biomedical concern, particularly for GI health and cancer risk. From plastic-laden seafood to polymer accumulation in tissues, environmental pollutants are infiltrating the human body with oncogenic consequences. The synergy between MNPs and established carcinogens is concerning, as alcohol, poor diet, and genetic predisposition compound malignancy risk through inflammation and impaired detoxification. These particles contribute to endocrine disruptors and heavy metals, exacerbating preexisting vulnerabilities. The epidemiological landscape remains nascent, requiring large-scale biomonitoring studies to delineate dose-response relationships and MNPs accumulation dynamics. Future research must integrate molecular toxicology, microbiomics, immunology, and oncology to understand MNPs’ health impact. Public health interventions should focus on exposure reduction through regulations, education, and sustainable packaging. Clinicians must stay vigilant when managing GI pathologies in high-exposure populations. Viewing MNPs as modifiable risk factors could potentially reduce the risk of GI cancer. The intersection of plastic pollution and GI malignancies shows that environmental health directly impacts human biology. To address this more clearly, data on MNPs’ effects requires both scientific research and evidence-based societal action.
Credit: David A. Johnson
Micro- and nanoplastics (MNPs) are emerging pollutants. Human exposure occurs mainly through ingestion of contaminated food and water and inhalation of airborne particles. MNPs can cross the intestinal barrier, accumulate in gastrointestinal (GI) tissues, and induce oxidative stress, DNA damage, inflammation, endocrine disruption, and gut dysbiosis—mechanisms relevant to carcinogenesis. The GI tract is particularly vulnerable due to direct mucosal contact and high epithelial turnover. Epidemiological evidence is limited, but early findings support a plausible link with GI cancers. As MNPs may be a modifiable risk factor, prevention should prioritize reduced plastic exposure, antioxidant-rich diets, and environmental monitoring.
Introduction
Plastic production has risen from 2 Mt in 1950 to a projected 1,200 Mt by 2060, with over 8,000 Mt of waste and <10% recycled. Microplastics are 1 µm–5 mm; nanoplastics are <1 µm. Primary MNPs are manufactured; secondary MNPs arise from breakdown of larger debris. Both persist for decades and enter food chains and water. Exposure routes include seafood, packaging, airborne fibers, and dermal contact, resulting in continuous low-dose exposure that may interact with other carcinogens.
Mechanisms and GI Accumulation
After ingestion, MNPs disrupt tight junctions and increase permeability, allowing particles and additives to translocate to the lamina propria, portal vein, liver, and lymph nodes. Key mechanisms include: (1) chronic low-grade inflammation via NF-κB; (2) oxidative stress and DNA damage; (3) gut dysbiosis with pro-inflammatory metabolites; and (4) endocrine-disrupting chemicals (bisphenol A, phthalates) exerting genotoxic effects.
MNPs are internalized by intestinal epithelial cells and retained during cell division, suggesting long-term persistence. They have been detected in blood, stool, colonic mucosa, and hepatic tissue, with higher loads in inflamed intestine and fibrotic liver.
Upper GI Carcinogenesis
MNPs are detectable in gastric tissue. Sub-micron particles provoke ROS and oxidative DNA damage, suppress DNA repair, and activate pro-proliferative signaling (MAPK, NF-κB). In esophageal models, polystyrene and PVC nanoplastics cause oxidative stress, DNA damage, apoptosis/pyroptosis, and barrier injury. In gastric cancer models, MNPs promote migration/invasion and epithelial–mesenchymal transition. Adsorbed co-contaminants (PAHs, plasticizers, metals) compound genotoxic signals. Human tumor data report microplastics within resected cancers and altered immune microenvironment. The plausibility chain is: exposure → mucosal uptake → oxidative/DNA damage and barrier failure → dysbiosis/inflammation → pro-oncogenic signaling.
Colorectal Cancer
Polystyrene particles have been found in human colorectal cancer tissues and promote progression and chemoresistance via autophagy activation (mTOR/ULK1). MNPs increase intestinal inflammation and dysbiosis. In vitro, they trigger mitochondrial ROS, NLRP3 inflammasome activation, and upregulate autophagy genes; they downregulate E-cadherin and upregulate Ki67, mimicking early transformation. Higher MNPs loads correlate with more aggressive phenotypes and chemoresistance.
Hepatocellular and Pancreatic Cancer
The liver is a primary deposition site. MNPs carry phthalates and bisphenols that activate PI3K/AKT/mTOR and Wnt/β-catenin pathways; PVC and polystyrene induce oxidative stress and DNA damage. In fibrotic livers, clearance is impaired and retention increased. PET microplastics disrupt lipid metabolism and elevate insulin, a precursor to steatotic liver disease and HCC. In pancreatic models, PET increases insulin resistance and pancreatitis, with mitochondrial dysfunction and NLRP3 activation implicated.
Gut Microbiome and Immune Surveillance
Dysbiosis reduces microbial diversity, favors pro-inflammatory taxa, and facilitates antigen translocation. It suppresses CD8⁺ T cells while promoting regulatory T cells and myeloid-derived suppressor cells. Microbial metabolites potentiate genotoxic stress. Impaired goblet cell function and MUC2 compromise the mucus barrier; elevated IL-6, TNF-α, and IL-1β sustain proliferation and inhibit apoptosis.
Carcinogenic Risk Factors
High-fat diets facilitate absorption of lipophilic pollutants and activate cytochrome P450 and aryl hydrocarbon receptor pathways. Genetic polymorphisms in GSTs and CYPs modulate vulnerability. Chronic inflammation creates a pro-tumorigenic microenvironment.
Minimization Strategies
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Reduce plastic use: promote biodegradable packaging, ban single-use plastics, restrict harmful additives.
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Filtration: ultrafiltration, reverse osmosis, and activated carbon reduce nanoplastics by up to 95%; boiling and filtering removes up to 90%.
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Public education: community outreach through schools, clinics, and media.
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Dietary changes: choose fresh whole foods; avoid microwaving in plastic; increase fiber, probiotics, and omega-3s.
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Regulation: align global standards and strengthen effluent limits.
Future Directions
Quantitative biomonitoring is needed to map particle types, sizes, and chemical payloads in human tissues. Large cohort studies should link dietary plastic intake with cancer outcomes. Mechanistic work should define dose thresholds and co-carcinogen interactions, and in vivo models should clarify chronic low-dose effects. Interdisciplinary efforts across environmental science, toxicology, microbiology, and oncology are essential.
Conclusions
MNPs are a pressing concern for GI health and cancer risk, interacting with established carcinogens to compound risk through inflammation and impaired detoxification. Epidemiological evidence remains nascent, requiring large-scale biomonitoring. Prevention should focus on exposure reduction through regulation, education, and sustainable packaging. Viewing MNPs as modifiable risk factors could help reduce GI cancer risk.
Full text
https://www.xiahepublishing.com/2994-8754/JTG-2025-00042
The study was recently published in the Journal of Translational Gastroenterology.
Journal of Translational Gastroenterology (JTG) dedicates to improving clinical diagnosis and treatment, advancing understanding of the molecular mechanisms, and promoting translation from bench to bedside of gastrointestinal, hepatobiliary, and pancreatic diseases. The aim of JTG is to provide a forum for the exchange of ideas and concepts on basic, translational, and clinical aspects of gastroenterology, and promote cross-disciplinary research and collaboration.
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