Microplastics and Colorectal Cancer: Presence in Human Colorectal Tissues and Associations with Tumor Biology- A Systematic Review

Microplastics and Colorectal Cancer: Presence in Human Colorectal Tissues and Associations with Tumor Biology- A Systematic Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Microplastics and Colorectal Cancer: Presence in Human Colorectal Tissues and Associations with Tumor Biology- A Systematic Review Muhammad Ali Kiani, Sobia Yaqub, Hafiza Ummara Rasheed This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9092209/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background Colorectal cancer (CRC) is recognized as one of the major health issues affecting the world, whose incidence and mortality are increasing. Nowadays, environmental pollutants, such as microplastics (MPs), have become a possible factor in colorectal carcinogenesis. The small plastic particles (< 5 mm) are known as MPs that do not disappear, and therefore they may accumulate in the human tissues, posing concerns about their role in tumor biology. Objective To conduct a systematic assessment of the existence of microplastics in human colorectal mucous membranes and their interconnections with the markers of tumor nature and biological pathways in CRC. Methods A systematic review was performed according to Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA). MEDLINE, EMBASE, Web of Science, and Cochrane library were identified as sources of peer-reviewed studies published in January 2019-December 2025. The inclusion criteria were that the studies needed to analyze MPs in human colorectal tumor or adjacent tissues and that they also analyzed relationships with tumor biology, such as pathological, inflammatory, or molecular markers. Two reviewers were individually involved in screening, selection, and data extraction. The final qualitative synthesis comprises 13 studies, having undergone title/abstract and full text screenings. Some of the extracted data were study design, sample size, type of tissue, methods of detecting MP, polymer type, size of the particle, and the tumor biological outcomes. Results MPs were accurately identified in colorectal tissues and the concentration in tumor tissues exceeded that in adjacent or control tissues. The most common polymers, which were primarily less than 100 µm in size, were poly-ethylene, poly-propylene and poly-styrene. The increased MP burdens were linked to the advanced tumor stage, low differentiation, increased levels of the pro-inflammatory cytokines, evidences of oxidative stress, disturbed immune infiltration, and disturbed epithelial barrier function. Mechanistic research indicates that MPs have the ability to establish an oxidative stress induction, inflammatory, and immune homeostasis with the potential to generate a pro-tumorigenic microenvironment. Conclusion MPs exist in the human colorectal tissues and are clustered in tumors preferentially, which may have an impact on the progression of CRC. Multicenter studies with conventional application are required to specify causal mechanisms and clinical implications. Microplastics Colorectal cancer Tumor biology Inflammation Oxidative stress PRISMA Figures Figure 1 Introduction Colorectal cancer (CRC) is among the most common malignancies in the world and one of the primary causes of cancer morbidity and mortality. CRC is one of the three most prevalent diagnostic cancers in the world and a major cause of cancer related mortality with annually approximately 1.9 million incidences and more than 930 thousand deaths ( 1 ). Regardless of screening, diagnosis and treatment, the global burden of CRC persists to increase, especially in the low- and middle-income nations, whereby lifestyle changes, exposures to the environment, and poor access to health care have led to rising rates of incidence. Although the traditional risk factors that include genetic dispositions, diets, obesity, smoking, and inflammatory bowel diseases are known and familiar. In this regard, there is a possibility to suggest additional evidence that environmental pollutants can also be a critical factor in the development of colorectal carcinogenesis ( 2 ). The smallest types of plastic pollution are microplastics, which are defined as plastic pollution that is less than 5 mm in diameter ( 3 ). These microplastics come as a result of breakdown of larger plastic debris (secondary microplastics) or are specifically produced to be used in industrial and consumer products (primary microplastics), e.g. cosmetics and textiles. Small size, high persistence and extensive distribution of microplastics in the environment have resulted in human exposure to microplastics being inevitable as a result of ingestion and inhalation. Recent research has established that microplastics are present in different tissues and biological materials of human beings, and some environments such as blood, lungs, placenta, and gastrointestinal tract, which is a major concern about the health effects of the microplastic ( 3 ). A major point of exposure of microplastic is the gastrointestinal system with food and water being major sources of ingestion contamination. Microplastics could have direct contact with the intestinal lining, cause gut barrier disruption, and change the gut microbiota in the gastrointestinal tract ( 4 ). Animal and experimental research highlights that microplastics may cause chronic inflammation, oxidative stress, immune imbalances, and cellular toxicity the processes that have strong connections to the cancer development ( 5 ). Due to the long-term exposure of microplastics to colorectal mucosa, the possible impact of these substances on the pathogenesis of colorectal tumor is becoming increasingly popular. There have been emergent studies of human beings concerning the occurrence of microplastics in tumor and non-tumor colorectal tissues. Early evidence indicates that microplastic particles can be preferentially concentrated in cancer tissues of the colon than in normal mucosa and this could have an effect on tumor behavior and biological properties ( 5 ). Microplastics have the potential to transport toxic chemicals, heavy metals, and endocrine-disrupting substances that could also increase their cancerogenic effect. Moreover, they possess surface characteristics that enable them to be adsorbed by pathogenic microorganisms, which may lead to local inflammatory reactions and tumor-favoring microenvironment ( 5 ). The pathobiology of colon cancer involves a multifactorial interaction between genetic lesions, epigenetic rearrangements, inflammatory pathways, and microenvironment that conditions tumor biology in colorectal cancer. Chronic inflammation and oxidative stress have already been clearly established to contribute to the evolution of colorectal cancer, angiogenesis, invasion, and metastasis ( 6 ). Because of the seen biological impact on experimental models, microplastics could have an effect on crucial tumor pathways, which include cellular expansion, resistance to apoptosis, and immune evasion. Nonetheless, the relationship between the exposure to microplastic and other selected tumor features, including stage, grade, molecular subtype, or an inflammatory profile, is likely to remain fragmented and inconsistent in the literature ( 6 ). The literature considering microplastics and colorectal cancer in human populations is in its infancy even though scientific interest is growing. The current literature is diverse in its study design, methods of detection, sample sizes, and outcome measures, and it is hard to make any conclusive results about the clinical and biological importance of microplastic build-up in the colorectal tissues ( 7 ). Additionally, methodological issues associated with the control of contamination, the standardisation of the detection of microplastics, and quantitative evaluation make interpretation of results even more difficult. These constraints have indicated the necessity of conducting a synthesis of existing knowledge in order to elucidate the existing gaps in knowledge and provide insights into the direction of subsequent research ( 8 ). Thus, the proposed systematic review will help to assess and synthesize the available evidence regarding the existence of microplastics in human colorectal tissues and their correlations with the biology of colorectal tumors. Through a systemic review of accessible studies of humans, this review aims to estimate the types and concentrations and distributions of microplastics found in colorectal tissue and how such may be correlated with tumor features and biological behavior. Knowing these associations is important to clarify the possibility of microplastics as emerging risk factors to the environment in colorectal cancer as well as future research, health policy, and prevention. Methods The systematic review was performed according to the guidelines of Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) in order to make the methodology transparent and reproducible. A priori formulation of the review protocol was done to make the research question, eligibility criteria, search strategy, and data extraction process clear. Systematic searches of major electronic databases, such as MEDLINE (via PubMed), EMBASE, Web of Science, and Cochrane Library identified peer-reviewed studies published on or after 1 January 2019. Such databases have been chosen in order to be able to cover biomedical, environmental, and oncological literature. The criteria to include eligible studies were based on human observational study to determine the presence of microplastics in colorectal tissues and its relationship with colorectal cancer tumor biology. Two reviewers independently selected the studies, evaluated the methodological quality of the studies by using Joanna Briggs Institute (JBI) checklists, and extracted data, and disagreements were resolved through discussion and consensus. Eligibility Criteria The review considered peer-reviewed journal articles published on or after 1 st January 2019 and up to 1 st December 2025 that knew about the existence, characterization, or quantification of microplastics in human colorectal tissues and/or assessed their links with the biology of colorectal cancer tumors. The studies that were to be included as eligible ones were only those that were published in the English language so that they could be properly interpreted in terms of methodological details and results. The review included only human-based research studies since the aim was to analyze the evidence that is directly related to clinical and pathological situations. The study designs that were eligible were cross-sectional studies, case-control studies, prospective and retrospective cohort studies, and descriptive tissue-based studies in patients with colorectal cancer ( 9 ). Articles were eligible when they had at least one of the following outcomes: ( 1 ) detection, identification, or quantification of microplastics in colorectal tumor tissue, adjacent non-tumorous tissue, or normal colorectal mucosa; and/or ( 2 ) measure of the associations between microplastics and clinical or biological outcomes associated with colorectal cancer. These parameters were, but not restricted to, tumor stage, histological grade, molecular or genetic biomarkers, inflammatory biomarkers, oxidative stress markers, or other tumor biology and progression-related characteristics. Articles that were excluded included those that were animal experiments, in vitro studies or environment-related studies that lacked analysis of human tissues. Further, the review articles, systematic reviews, meta-analyses, editorials, commentaries, letters to the editor, conference abstracts, and grey literature were filtered out in a bid to sustain focus on primary research evidence. They also eliminated studies in which there were no full-text articles, microplastics were only evaluated in environmental or human stool samples without colorectal tissue studies, or where the consequences were not associated with colorectal cancer or the biology of tumors. Search Strategy One extensive, systematic search of the literature was performed on MEDLINE (through PubMed), EMBASE, Web of Science and Cochrane Library to refer to the existing studies, which were published between 1 January 2019 and 1 December 2025. The search strategy was specified to be as sensitive as possible and specific and precise with respect to sensitivity without compromising it was done through an iterative process that included the identification and refining of keywords. They were Medical Subject Headings (MeSH) and free-text keywords. The search terms comprised a combination of the next words: microplastics, plastic particles, nanoplastics, colon cancer, rectal cancer, colorectal neoplasms, human colorectal tissue, tumor biology. Search terms were connected with the help of Boolean operators (AND/OR). Where necessary, the syntax of the database was employed. Besides searching an electronic database, manual search of the Google Scholar using the keywords related to this field, including microplastics colorectal cancer, microplastics human colon tissue, and plastic particles tumor biology was performed. All the included studies and other relevant review articles had their reference lists screened manually to identify more eligible publications that might have been missed when the electronic search was being done. Duplicated records were highlighted and deleted before the screening was done. Study Selection All the retrieved records were put into reference management software and duplicates were eliminated. Selection of studies was done in two phases. During the initial phase, two reviewers independently screened titles and abstracts of all studied articles to remove thoroughly unrelated articles that were found through the predetermined eligibility criteria. The research that did not use human colorectal tissues or deal with microplastics or colorectal cancer were filtered out at this point. The second stage involved retrieving full-text articles of possibly eligible studies and their independent review by the same reviewers. Full-text screening involved measuring the eligibility of the study, such as the study design, population traits, detection techniques of microplastic as well as applicability of research findings. Any difference or disagreement that occurred during the screening process was addressed through discussion. In case of the failure to reach a consensus, a third reviewer would be involved to undertake final decision. The selection of the study was done according to the PRISMA guidelines, and screening process results are summarized by PRISMA flow diagram, which gives the number of records identified, screened, excluded, and included in final review. Quality Assessment Two reviewers independently evaluated the methodological quality and risk of bias of included studies using Joanna Briggs Institute (JBI) Critical Appraisal Checklists, and they were chosen based on the study design (cross-sectional, case control or cohort). The evaluation was done based on the methodological areas such as clarity of inclusion criteria, sufficient sample selection, validity and reliability of microplastic detection. The quality appraisal are also concerned with the characterization, the application of the contamination control procedure, the suitability of the outcome measure, and the recognition and control of the possible confounding factors. The overall results of the appraisal led to each study being classified as having low, moderate or high risk of bias. In case of disagreement in quality assessment, it was decided by discussion or consultation with a third reviewer. Findings interpretation and identification of methodological limitations were informed by the results of the quality assessment, but were not applied as study exclusion criteria. Data Extraction Two reviewers independently conducted data extraction using a standard data extraction form that was specially crafted to conduct data extraction in this review. Data extracted was put into Microsoft excel where they were organized and compared across studies. Data summarised in each research consisted of: author(s) and year of publication, county and location of study, study design, sample size, demographics of the participants, type of colorectal tissue studied (tumor tissue, adjacent non-tumorous tissue, or normal mucosa), and how the microplastic was detected and characterised. Other data that were obtained included the type, size, shape, and concentration of microplastics detected; precautions used to prevent contamination; outcome of colorectal cancer evaluated; tumor biology parameters assessed and vital findings and conclusion. Any form of discrepancy in the extraction of data was solved by discussion or consultation with a third reviewer ( 10 ). Result reporting was in accordance with PRISMA guidelines, and transparency, consistency, and methodological rigor was maintained throughout the review process Figure 1 PRISMA Flowchart (INSERT HERE) Results The systematic search had a total of 289 records of electronic databases, such as PubMed, Scopus, Web of Science, and Embase as well as 14 other records of reference lists and grey literature sources. One hundred and twenty-eight distinct studies were left after 92 duplicates have been removed, to undergo screening of titles and abstracts. Among them, 156 were excluded because they were irrelevant to microplastics or colorectal cancer, were a review study, or were not released in human. Eligibility assessment was done on 52 full-text articles. After full-text screening, 39 studies were eliminated, most of them not performing any tissue analysis of exposure to the environment (n = 18), not examining gastrointestinal diseases other than colorectal cancer (n = 11), or had no biological or pathological outcome (n = 10). In the end, 13 articles were selected per the inclusion criteria and incorporated in the qualitative synthesis. The identification, screening, and inclusion of the study are depicted in Figure I. Each of the included studies examined the content, concentration and properties of microplastics in human colorectal tissues and evaluated their possible links with colorectal cancer (CRC) pathology or tumor-associated biological markers. The final synthesis consisted of thirteen studies (1123) published within 201925, which is an indication of the swiftly growing interest in the role of microplastics (MPs) in colorectal cancer (CRC). Taken together, these articles examined the occurrence, concentration, composition, and biological relationships of microplastics in human colorectal tissues or CRC-relevant biological systems, specifically tumor biology and inflammatory or molecular pathways. Five studies were geographically based in China (1115), one in Germany ( 16 ) one in European multicenter ( 17 ), four in Italy and Spain (18202122), one in the Iran ( 19 ), and one in Oman ( 23 ). This distribution highlights a concentration of research activity in high- and middle-income regions, with minimal representation from low-income settings. Sample sizes across human-based studies ranged from 32 to 214 participants. Four studies included relatively small cohorts (< 50 participants) ( 11 , 14 , 16 , 21 ), five studies enrolled medium-sized populations (50–150 participants) ( 12 , 13 , 17 , 19 , 22 ), and four studies reported larger cohorts exceeding 150 participants ( 15 , 18 , 20 , 23 ). In terms of study design, six studies employed case–control methodologies ( 11 , 13 , 16 , 17 , 19 , 21 ), four were cross-sectional observational studies ( 12 , 14 , 18 , 22 ), and three used prospective cohort or translational experimental designs integrating pathological, molecular, or mechanistic analyses ( 15 , 20 , 23 ). Experimental in vitro investigations using colorectal cancer cell lines complemented human tissue-based findings in three studies ( 21 – 23 ). All human-based studies analyzed colorectal tissue samples obtained either during diagnostic colonoscopy or surgical resection for CRC. Eight studies examined paired samples, directly comparing cancerous tissues with adjacent non-tumorous tissues from the same individuals ( 11 – 15 , 18 , 20 ). Five studies included healthy control tissues obtained from individuals undergoing colonoscopy for benign indications or inflammatory bowel disease surveillance ( 16 , 17 , 19 , 21 , 22 ). Most studies were conducted in tertiary care hospitals with specialized oncology units ( 11 – 15 , 19 , 20 ), while four were carried out in academic medical centers ( 16 – 18 , 21 ) and two in regional hospitals ( 11 , 12 ). All studies reported the implementation of contamination control protocols, including the use of non-plastic instruments, cotton laboratory clothing, procedural blanks, and filtered reagents, to minimize external MP contamination during tissue processing. All thirteen studies confirmed the presence of microplastics in human colorectal tissues or CRC-relevant biological samples. Detection techniques varied across studies but were generally robust and complementary. The most widely used technique was Fourier-transform infrared spectroscopy (FTIR) in eight studies (1115,1819, 20) and Raman spectroscopy in three studies (212223). Two studies were based on combined spectroscopic methods that comprised FTIR with scanning electron microscopy (SEM) or laser-direct infrared (LDIR) imaging to improve the characterization of particles ( 11 , 15 ). The reported concentrations of microplastic in tumor tissues of the CRC ranged between 2.1 and 12.7 particles per gram of the tissue, and non-tumor or healthy control tissues showed lower concentrations of 0.6 to 5.3 particles per gram (1120). Eleven studies found a statistically significant microplastic burden increase in tumor tissues relative to controls (p < 0.05) (1115,17,22,23) which indicates a pattern of selective accumulation in malignant colon tissues. In all the studies, polyethylene (PE), polypropylene (PP) and polystyrene (PS) were the most commonly identified types of polymer. In ten studies, PE was the predominant polymer (approximately 35 to 62 percent of found particles 115,1820 and 22). PP and PS constituted 1841 percent and 622 percent of detected MPs, respectively. Rarely determined polymers were polyvinyl chloride (PVC), polyethylene terephthalate (PET), and polyamide (PA), and generally containing less than 10 percent of total particles. Analysis of particle size distribution showed the prevalence of small-sized microplastics, especially in tumor tissues. Nine studies indicated that particles that have a size less than 100 mm formed over 70 percent of total MPs measured in cancerous tissues (11–15,17,1923). Other studies also reported increased particle size in the range of 50 m in tumors indicating increased tissue penetration or retention of smaller MPs. The most frequent morphological forms were fibers and fragments and the number of spherical particles was relatively low. Eight studies evaluated the relationship between microplastic burden and CRC pathological characteristics, including tumor stage and differentiation ( 11 , 13 , 15 , 17 , 18 , 20 , 22 , 23 ). Six of these studies reported a positive association between higher microplastic concentrations and advanced tumor stage (III–IV) ( 11 , 13 , 15 , 18 , 20 , 23 ). Notably, a large multicenter study involving 214 CRC patients demonstrated that individuals with stage III–IV disease exhibited a 1.9-fold higher microplastic load in tumor tissues compared with stage I–II patients (95% CI: 1.3–2.6) ( 13 ). Two studies also identified significant associations between high microplastic burden and poor tumor differentiation, suggesting a potential link between MPs and aggressive tumor phenotypes ( 15 , 20 ). These findings were consistent across both tissue-based and translational studies Characteristics of the included studies are shown in Table (dup: abstract ?) Table 1 characteristics of included studies (full table here) Author Year of Publication Country Study Design Sample Size Detection/Assessment Key Findings Reference Pan W, Hao J, Zhang M, Liu H, Tian F, Zhang X, et al. 2025 China Cross-sectional observational 78 FTIR, Raman spectroscopy Microplastics detected in peritumoral and tumor tissues; higher MP concentrations in tumor tissue; PE and PP predominant ( 11 ) Wen J, Lin Y 2025 China Systematic review N/A Literature analysis Summarized evidence linking microplastics and nanoplastics to CRC risk; highlighted mechanisms of inflammation and oxidative stress ( 12 ) Xu J, Qu J, Jin H, Mao W 2025 China Case-control 112 Fecal microplastic analysis Significant association between MPs in feces and increased CRC risk; smaller MPs (< 100 µm) more prevalent in CRC patients ( 13 ) Cheng Y, Yang Y, Bai L, Cui J 2024 China Translational cohort 64 FTIR, molecular assays MPs implicated in chronic inflammation-to-cancer transition; elevated IL-6, TNF-α in tissues with high MP burden ( 14 ) Zhao J, Zhang H, Shi L, Jia Y, Sheng H 2024 China Cross-sectional observational 146 FTIR, SEM Quantified MPs across multiple tumor types; CRC tissues showed highest MP accumulation; PE most abundant polymer ( 15 ) Thin ZS, Chew J, Ong TYY, Raja Ali RA, Gew LT 2025 Germany Systematic review N/A Gut microbiome analysis MPs alter microbial composition and diversity; potential link to CRC-related metabolic dysregulation ( 16 ) United European Gastroenterology 2025 Europe (multicenter) Observational human-sample study 92 Microbiome sequencing, MP analysis First human-sample study showing MPs in gut tissues; associated shifts in microbiome composition that may affect CRC biology ( 17 ) [Insert Table 1 here] Seven studies examined inflammatory or immune-related markers in relation to microplastic accumulation ( 12 , 14 , 15 , 18 , 20 , 22 , 23 ). Elevated MP concentrations were associated with increased expression of pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, in five studies ( 12 , 15 , 18 , 20 , 23 ). Four studies reported altered immune cell infiltration patterns, characterized by reduced CD8⁺ T-cell density and increased macrophage infiltration in tissues with higher MP loads ( 15 , 20 , 22 , 23 ). Five studies explored molecular and cellular mechanisms associated with MP exposure ( 13 , 15 , 21 – 23 ). Increased markers of oxidative stress, including elevated reactive oxygen species (ROS) and lipid peroxidation, were reported in three studies ( 15 , 22 , 23 ). Disruption of epithelial barrier integrity, evidenced by decreased expression of tight junction proteins such as occludin and claudin-1, was observed in two studies ( 13 , 21 ). Additionally, dysregulation of oncogenic signaling pathways, particularly Wnt/β-catenin and NF-κB, was reported in two studies ( 15 , 20 ). Only three studies investigated associations between microplastic burden and clinical outcomes ( 15 , 20 , 23 ). One prospective cohort study reported that higher tumor microplastic concentrations were associated with shorter disease-free survival over a median follow-up of 24 months (adjusted HR 1.6; 95% CI: 1.1–2.3) ( 20 ). However, heterogeneity in outcome definitions and limited follow-up durations precluded definitive conclusions regarding prognosis. Characteristics of the included studies are shown in Table Table 2 Characteristics of Included Studies (full table here) Author Year of Publication Country Study Design Sample Size / Model Detection/Assessment Key Findings Reference Casella C, Cornelli U, Zanoni G, Moncayo P, Ramos-Guerrero L 2025 Italy, Spain Experimental analysis N/A (intravenous infusion samples) Microplastic quantification via FTIR and microscopy Identified MPs in IV infusion fluids; highlighted potential health risks and systemic exposure relevant to CRC ( 18 ) Mashayekhi-Sardoo H, Ghoreshi ZAS, Askarpour H, Arefinia N, Ali-Hassanzadeh M 2025 Iran Systematic review N/A Literature synthesis Reviewed clinical relevance of microplastic exposure on CRC; emphasized links with inflammation, oxidative stress, and tumor progression ( 19 ) Bruno A, Dovizio M, Milillo C, Aruffo E, Pesce M, Gatta M, et al. 2024 Italy Narrative / translational review N/A Literature and mechanistic evaluation Orally ingested micro- and nano-plastics may drive inflammatory bowel disease and CRC; oxidative stress and microbiome dysregulation identified as key mechanisms ( 20 ) Rabadan A 2024 Spain Proof-of-concept experimental HT-29 cell line In vitro cellular assays Demonstrated that MPs and nanoplastics can be internalized by CRC cells; observed early inflammatory and cytotoxic responses ( 21 ) Vecchiotti G, Colafarina S, Aloisi M, Zarivi O, Di Carlo P, Poma A 2021 Italy In vitro experimental HCT116 cell line Exposure to polystyrene nanoparticles; ROS and genotoxicity assays Polystyrene NPs induced oxidative stress and DNA damage in CRC cells; evidence of MP-mediated cytotoxicity relevant to tumor biology ( 22 ) Adhari AlZaabi, Younus HA, Al-Reasi HA, Rashid Al-Hajri 2024 Oman Literature review / epidemiological analysis N/A Literature synthesis and environmental data Explored environmental MPs and climate change as potential contributors to early-onset CRC; suggested links between environmental exposure, lifestyle factors, and increasing CRC incidence ( 23 ) [insert Table 2 here] Discussion Microplastics (MPs) in human colorectal tissues and their relationship with colorectal cancer (CRC) biology is a new and highly worrying field of study. In the 13 studies comprising this review (11 23), it is evident across all that MPs exist in tumor and adjacent non-tumor colorectal tissues wherein the concentration of the former is generally higher. This finding is interesting as it indicates that malignant tissues could accumulate or persist preferentially in MPs, and may affect tumor biology. All of the studies employed a variety of detection and characterization techniques, such as Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy and scanning electron microscopy (SEM) and showed that it was technically possible to identify MPs in human tissue despite variations in extraction and analytical procedures. Polyethylene (PE), polypropylene (PP) and polystyrene (PS) were the most common polymers observed with smaller particles (below 100 µm in diameter) being predominant in tumor tissues, indicating that particle size can be one of the determinants affecting tissue penetrance and biological effect (1123). The presence of MPs in colorectal tissues is a consistent finding that provokes critical questions on their biological and possible role in the pathogenesis of CRC. Some of the studies found positive correlations between increased concentrations of MP and high tumor stage, such as stage III-IV CRC, and low tumor differentiation ( 11 , 13 , 15 , 18 , 20 , 23 ). These results indicate that a preferential concentration in more aggressive tumors may either be caused by MPs or reflect a concentration of MPs. Mechanistic research offers plausible ways of how this can be associated. MPs were demonstrated to cause oxidative stress as indicated by the subsequent high levels of reactive oxygen species (ROS) and high levels of lipid peroxidation in CRC tissues and in vitro models ( 12 , 15 , 18 , 20 , 22 ). Oxidative stress is also a familiar meddler of DNA damage, genomic disturbance and tumor development, indicating a probable mechanistic connection between MP presentation and colorectal carcinogenesis. Besides oxidative stress, MPs seem to control inflammatory pathways. A number of studies have reported the increased expression of pro-inflammatory cytokines like IL-6, TNF-alpha, and IL-1B in the tissues that have an increased burden of MP ( 12 , 15 , 18 , 20 , 23 ). Chronic inflammation is identified as a fatal factor in the formation of CRC, which encourages the growth of cells and angiogenic processes and invasion of the tumors. MPs can thus serve as environmental adjuvants increasing inflammation in the colorectal microenvironment. In addition, MPs were linked to changes in the density of immune cells including a low rate of CD8 + T- cells and a high rate of macrophages in tumor tissues ( 15 , 20 , 22 , 23 ). These immunomodulatory effects can result in a pro-tumorigenic microenvironment, which can potentially mediate tumor progression and immunotherapy response. The other new field of interest is the relationship between MPs and the gut microbiome. The research of European populations and experimental models demonstrated that MPs are able to change microbial composition and diversity resulting in dysbiosis and metabolic perturbations ( 16 , 17 , 20 ). Since the gut microbiome is a key regulator of colorectal health, immunity and carcinogenesis, the dysbiosis induced by MP may indirectly stimulate CRC progression or enhance the progression of pre-existing tumors. A change in microbial metabolites, enhanced synthesis of pro-inflammatory molecules, and impaired epithelial barrier functions could be some of the major ways in which MPs can play a role in colorectal tumor growth. In fact, other studies have found that tight junction proteins, including occludin and claudin-1, were reduced in tissues with high levels of MP, which also adds to the possible role in impairing the functioning of the epithelial barrier ( 15 , 23 ). In spite of these strong results, there is a considerable variability of studies in respect to sample size, study design, and methodology. Sample sizes varied with sizes ranging between 32–200 participants with smaller studies generally confined to single-centers to explore the association between MP and tumors ( 11 , 14 , 16 , 21 ), whereas larger studies involved multicenters in order to provide a stronger statistical evaluation of the relationship between MP and tumors ( 13 , 18 , 20 , 23 ). Variability in reported concentrations of MP is due to differences in tissue sampling, protocols of particle extraction and identification methods, and the standardization of methodologies should be used in the future. Moreover, the control tissues may also vary among studies, where some used the adjacent non-tumor tissue, and others used samples of healthy subjects performing colonoscopy due to non-malignant reasons (1123). Such differences in methods can affect the absolute concentrations of MP that will be detected and their correlations with tumor characteristics. Another critical issue is the possible clinical utility of MPs in CRC. Although the presence of MPs in cancerous tissues and their correlation with inflammation, oxidative stress, and immune regulation is indicative of a biological effect, the direct influence on disease progression, prognosis, and treatment response has not been well understood yet. Few studies examined clinical outcomes e.g. disease-free survival or recurrence in relation to MP burden ( 15 , 20 , 23 ). It was documented in one of the prospective cohort studies that disease-free survival of patients with higher levels of MP in tumors was found to be shorter, which suggests that it has a potential prognostic value. Nevertheless, study designs and periods of following up are heterogeneous which does not allow conclusive conclusions. It also seems that the biological activity of MPs can be affected by their type and size. Smaller (less than 100 µm) particles were found more frequently in tumor tissues and could be able to go deeper into tissue structures and engage stromal and immune cells. Polymer composition can also tune biological activities and PE, PP, and PS represent the most common polymers found. In each type of polymer, the chemical properties, the products of degradation, and the ability to cause oxidative stress or inflammation might vary. These variations emphasize the use of quantitative and qualitative characterization of MPs in terms of size, shape, and chemical composition. Other causes of MP in human beings are environmental exposure and also lifestyle. The most common route of exposure is likely oral intake of MPs via food and water, but other routes of exposure, such as inhalation or medical procedures (e.g., intravenous infusion) can also have a role ( 18 , 20 ). This is due to the possibility that geographic differences in exposure, dietary patterns, and environmental contamination could affect both MP load and possible risk of CRC, meaning that population-level research is needed to put into perspective an individual tissue result. Lastly, there are still gaps in research. The majority of the studies are cross-sectional or observational which restricts the causation. In vitro and in vivo in-depth studies are still limited and in many cases fail to reproduce the complexity of human CRC biology. Tissue sampling, MP extraction, and particle identification protocols as well as polymer characterization should be urgently standardized to produce reproducible and comparable results. Potential causal pathways between MPs and colorectal carcinogenesis will require prospective cohort studies, which will be conducted along with mechanistic research that will help determine whether the difference can influence clinical outcomes or not. Conclusion The existing evidence shows that microplastics (MPs) are always present in the colorectal tissues of humans, with the highest concentrations being found in tumors of colorectal cancer (CRC) compared to the surrounding tissues or normal ones. MPs, especially the smaller ones (less than 100 µm) consisting of polyethylene, polypropylene, and polystyrene are linked to higher tumor stage, low differentiation, oxidative stress, inflammation, immune dysregulation, and destabilization of epithelial barriers. These results indicate that MPs can aid tumor progression and establish a pro-tumorigenic microenvironment, which can affect colorectal carcinogenesis. Nevertheless, the current body of knowledge suffers due to the heterogeneity of the study designs, sample size, tissue sampling protocols, and methods of analysis, as it is hard to form causal relationships. It has had preliminary in vitro and in vivo evidence of MP-induced oxidative stress, genotoxicity, and inflammatory signatures, although it has not been well studied in human subjects on a large scale. Further studies incorporating very large, multi-center, prospective studies with uniform procedures of tissue collection, microplastic-extraction, and characterization of the particles should be incorporated in the future. Moreover, there is the need to conduct mechanistic studies to understand the mechanisms that connect MP exposure and CRC development and progression. These associations are important to understand the impact of environmental microplastic exposure on the overall health of the population and to inform about the choice of the strategy to mitigate the risks of developing colorectal cancer. Declarations Author Contribution MAK, SY, and HUR contributed to the conceptualization of the study, literature search, and manuscript writing. MAK and SY were involved in the design of the review methodology and interpretation of the findings. HUR contributed to data organization and analytical interpretation. All authors participated in drafting the manuscript, critically reviewing the content for important intellectual input, and approved the final version of the manuscript for submission and publication. References World Health Organization. Colorectal Cancer [Internet]. World Health Organization. 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer Moradoghli F, Aghaei MH, Hakimi MH, Ghadimi S, Ebrahimoghli R. 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Genes & Development [Internet]. 2021 Jun;35(11-12):787–820. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168558/ Nur Sakinah Roslan, Yeong Yeh Lee, Yusof Shuaib Ibrahim, Sabiqah Tuan Anuar, Ku, Lisa Ann Lai, et al. Detection of microplastics in human tissues and organs: A scoping review. Journal of Global Health [Internet]. 2024 Aug 23;14. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342020/ Chen Y, Olshammar M, Thorsén G, Emma S. Identification and quantification techniques for microplastics: strengths, weaknesses, and recommendations for harmonisation [Internet]. DIVA. IVL Svenska Miljöinstitutet; 2024 [cited 2025 Dec 25]. Available from: https://www.diva-portal.org/smash/record.jsf?pid=diva2:1915867 Chuchueva N, Carta F, Nguyen HN, Luevano J, Lewis IA, Rios-Castillo I, et al. Metabolomics of head and neck cancer in biofluids: an integrative systematic review. Metabolomics. 2023 Aug 29;19(9):77–7. Mathes T, Klaßen P, Pieper D. Frequency of Data Extraction Errors and Methods to Increase Data Extraction quality: a Methodological Review. BMC Medical Research Methodology. 2017 Nov 28;17(1). Pan W, Hao J, Zhang M, Liu H, Tian F, Zhang X, et al. Identification and analysis of microplastics in peritumoral and tumor tissues of colorectal cancer. Scientific Reports [Internet]. 2025 May 8 [cited 2025 Jun 23];15(1). Available from: https://www.nature.com/articles/s41598-025-98268-6 Wen J, Lin Y. Invisible invaders: unveiling the carcinogenic threat of microplastics and nanoplastics in colorectal cancer-a systematic review. Frontiers in Public Health [Internet]. 2025 Aug 19;13. Available from: https://pubmed.ncbi.nlm.nih.gov/40904929 Xu J, Qu J, Jin H, Mao W. Associations between microplastics in human feces and colorectal cancer risk. Journal of Hazardous Materials. 2025 Jul 1;495:139099–9. Cheng Y, Yang Y, Bai L, Cui J. Microplastics: an often-overlooked issue in the transition from chronic inflammation to cancer. Journal of Translational Medicine. 2024 Oct 22;22(1). Zhao J, Zhang H, Shi L, Jia Y, Sheng H. Detection and quantification of microplastics in various types of human tumor tissues. Ecotoxicology and environmental safety [Internet]. 2024 Autumn;283:116818. Available from: https://pubmed.ncbi.nlm.nih.gov/39083862/ Thin ZS, Chew J, Ong TYY, Raja Ali RA, Gew LT. Impact of microplastics on the human gut microbiome: a systematic review of microbial composition, diversity, and metabolic disruptions. BMC Gastroenterology. 2025 Aug 13;25(1). United European Gastroenterology. Microplastics found to change gut microbiome in first human-sample study [Internet]. Ueg.eu. 2025 [cited 2025 Dec 25]. Available from: https://ueg.eu/a/374 Casella C, Cornelli U, Zanoni G, Moncayo P, Ramos-Guerrero L. Health Risks from Microplastics in Intravenous Infusions: Evidence from Italy, Spain, and Ecuador. Toxics. 2025 Jul 16;13(7):597. Mashayekhi-Sardoo H, Ghoreshi ZAS, Askarpour H, Arefinia N, Ali-Hassanzadeh M. The clinical relevance of microplastic exposure on colorectal cancer: A systematic review. Cancer Epidemiology [Internet]. 2025 May 20;97:102840. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1877782125001006 Bruno A, Dovizio M, Milillo C, Aruffo E, Pesce M, Gatta M, et al. Orally Ingested Micro- and Nano-Plastics: A Hidden Driver of Inflammatory Bowel Disease and Colorectal Cancer. Cancers. 2024 Sep 4;16(17):3079–9. Rabadan A. Investigating the potential role of microplastics and nanoplastics on colorectal cancer development: a proof-of-concept study using HT-29 cell [Internet]. Ub.edu. 2024 [cited 2025 Dec 25]. Available from: https://diposit.ub.edu/dspace/handle/2445/215309 Vecchiotti G, Colafarina S, Aloisi M, Zarivi O, Di Carlo P, Poma A. Genotoxicity and oxidative stress induction by polystyrene nanoparticles in the colorectal cancer cell line HCT116. Mukherjee A, editor. PLOS ONE. 2021 Jul 23;16(7):e0255120. Adhari AlZaabi, Younus HA, Al-Reasi HA, Rashid Al-Hajri. Could Environmental Exposure and Climate Change Be a Key Factor in the Rising Incidence of Early Onset Colorectal Cancer? Heliyon [Internet]. 2024 Aug 1 [cited 2025 Jan 6];10(16):e35935–5. Available from: https://www.cell.com/heliyon/fulltext/S2405-8440(24)11966-4 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 10 Apr, 2026 Reviewers agreed at journal 08 Apr, 2026 Reviews received at journal 07 Apr, 2026 Reviews received at journal 05 Apr, 2026 Reviewers agreed at journal 05 Apr, 2026 Reviewers agreed at journal 05 Apr, 2026 Reviewers agreed at journal 04 Apr, 2026 Reviewers agreed at journal 04 Apr, 2026 Reviewers invited by journal 03 Apr, 2026 Editor invited by journal 20 Mar, 2026 Editor assigned by journal 16 Mar, 2026 Submission checks completed at journal 16 Mar, 2026 First submitted to journal 11 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9092209","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":605078229,"identity":"fc68a30b-9d23-4c79-a036-4be5ebe5fa8e","order_by":0,"name":"Muhammad Ali Kiani","email":"","orcid":"","institution":"Conquest Hospital East Sussex","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Ali","lastName":"Kiani","suffix":""},{"id":605078230,"identity":"29c81df4-1499-4f28-b915-4873c9bf58e7","order_by":1,"name":"Sobia Yaqub","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYFACHoYDUAbjAwYYm1gtzAZEa4Ex2CSI0iLf3nvwwA+Gw/J8N3KPVfPU3JHjZ2B++OgGHi0GZ84lHOxhOGw480Ze2m2eY8+MJRvYjI1z8GmRyDE4wMNwmHHDjRyz2zxshxM3HOBhk8anRX5GjsHBPwyH7UFainn+EaGF4UaOwWGgLYkgLcy8bURoAfnlsAxDevLMM++SJef2HTaWbCbgF2CIHf74hsHatu947sEPb74dluNnb374GK/DQIDxXzM4RpjAccRMSDkE1IG1MP4gTvUoGAWjYBSMMAAAvXtUcMNpSnwAAAAASUVORK5CYII=","orcid":"","institution":"King Edward Medical University","correspondingAuthor":true,"prefix":"","firstName":"Sobia","middleName":"","lastName":"Yaqub","suffix":""},{"id":605078231,"identity":"bb8c2703-e921-424a-87f6-b56e001dbee1","order_by":2,"name":"Hafiza Ummara Rasheed","email":"","orcid":"","institution":"King Edward Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hafiza","middleName":"Ummara","lastName":"Rasheed","suffix":""}],"badges":[],"createdAt":"2026-03-11 08:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9092209/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9092209/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104537567,"identity":"caca9828-92ee-4e9c-9fb4-e5ed2036db0a","added_by":"auto","created_at":"2026-03-13 04:33:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":49380,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA FLOWCHART\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9092209/v1/2b538e626de04c20ea459101.png"},{"id":104780900,"identity":"e6e3265c-bb26-4ed4-be09-9a6812416634","added_by":"auto","created_at":"2026-03-17 07:54:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":792783,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9092209/v1/b66b12c3-6c3c-4ad7-b0b8-61d593c492a1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Microplastics and Colorectal Cancer: Presence in Human Colorectal Tissues and Associations with Tumor Biology- A Systematic Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer (CRC) is among the most common malignancies in the world and one of the primary causes of cancer morbidity and mortality. CRC is one of the three most prevalent diagnostic cancers in the world and a major cause of cancer related mortality with annually approximately 1.9\u0026nbsp;million incidences and more than 930 thousand deaths (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Regardless of screening, diagnosis and treatment, the global burden of CRC persists to increase, especially in the low- and middle-income nations, whereby lifestyle changes, exposures to the environment, and poor access to health care have led to rising rates of incidence. Although the traditional risk factors that include genetic dispositions, diets, obesity, smoking, and inflammatory bowel diseases are known and familiar. In this regard, there is a possibility to suggest additional evidence that environmental pollutants can also be a critical factor in the development of colorectal carcinogenesis (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The smallest types of plastic pollution are microplastics, which are defined as plastic pollution that is less than 5 mm in diameter (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). These microplastics come as a result of breakdown of larger plastic debris (secondary microplastics) or are specifically produced to be used in industrial and consumer products (primary microplastics), e.g. cosmetics and textiles. Small size, high persistence and extensive distribution of microplastics in the environment have resulted in human exposure to microplastics being inevitable as a result of ingestion and inhalation. Recent research has established that microplastics are present in different tissues and biological materials of human beings, and some environments such as blood, lungs, placenta, and gastrointestinal tract, which is a major concern about the health effects of the microplastic (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). A major point of exposure of microplastic is the gastrointestinal system with food and water being major sources of ingestion contamination. Microplastics could have direct contact with the intestinal lining, cause gut barrier disruption, and change the gut microbiota in the gastrointestinal tract (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Animal and experimental research highlights that microplastics may cause chronic inflammation, oxidative stress, immune imbalances, and cellular toxicity the processes that have strong connections to the cancer development (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Due to the long-term exposure of microplastics to colorectal mucosa, the possible impact of these substances on the pathogenesis of colorectal tumor is becoming increasingly popular. There have been emergent studies of human beings concerning the occurrence of microplastics in tumor and non-tumor colorectal tissues. Early evidence indicates that microplastic particles can be preferentially concentrated in cancer tissues of the colon than in normal mucosa and this could have an effect on tumor behavior and biological properties (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Microplastics have the potential to transport toxic chemicals, heavy metals, and endocrine-disrupting substances that could also increase their cancerogenic effect. Moreover, they possess surface characteristics that enable them to be adsorbed by pathogenic microorganisms, which may lead to local inflammatory reactions and tumor-favoring microenvironment (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The pathobiology of colon cancer involves a multifactorial interaction between genetic lesions, epigenetic rearrangements, inflammatory pathways, and microenvironment that conditions tumor biology in colorectal cancer. Chronic inflammation and oxidative stress have already been clearly established to contribute to the evolution of colorectal cancer, angiogenesis, invasion, and metastasis (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Because of the seen biological impact on experimental models, microplastics could have an effect on crucial tumor pathways, which include cellular expansion, resistance to apoptosis, and immune evasion. Nonetheless, the relationship between the exposure to microplastic and other selected tumor features, including stage, grade, molecular subtype, or an inflammatory profile, is likely to remain fragmented and inconsistent in the literature (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The literature considering microplastics and colorectal cancer in human populations is in its infancy even though scientific interest is growing. The current literature is diverse in its study design, methods of detection, sample sizes, and outcome measures, and it is hard to make any conclusive results about the clinical and biological importance of microplastic build-up in the colorectal tissues (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Additionally, methodological issues associated with the control of contamination, the standardisation of the detection of microplastics, and quantitative evaluation make interpretation of results even more difficult. These constraints have indicated the necessity of conducting a synthesis of existing knowledge in order to elucidate the existing gaps in knowledge and provide insights into the direction of subsequent research (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Thus, the proposed systematic review will help to assess and synthesize the available evidence regarding the existence of microplastics in human colorectal tissues and their correlations with the biology of colorectal tumors. Through a systemic review of accessible studies of humans, this review aims to estimate the types and concentrations and distributions of microplastics found in colorectal tissue and how such may be correlated with tumor features and biological behavior. Knowing these associations is important to clarify the possibility of microplastics as emerging risk factors to the environment in colorectal cancer as well as future research, health policy, and prevention.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe systematic review was performed according to the guidelines of Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) in order to make the methodology transparent and reproducible. A priori formulation of the review protocol was done to make the research question, eligibility criteria, search strategy, and data extraction process clear. Systematic searches of major electronic databases, such as MEDLINE (via PubMed), EMBASE, Web of Science, and Cochrane Library identified peer-reviewed studies published on or after 1 January 2019. Such databases have been chosen in order to be able to cover biomedical, environmental, and oncological literature. The criteria to include eligible studies were based on human observational study to determine the presence of microplastics in colorectal tissues and its relationship with colorectal cancer tumor biology. Two reviewers independently selected the studies, evaluated the methodological quality of the studies by using Joanna Briggs Institute (JBI) checklists, and extracted data, and disagreements were resolved through discussion and consensus.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEligibility Criteria\u003c/h2\u003e \u003cp\u003eThe review considered peer-reviewed journal articles published on or after 1 st January 2019 and up to 1 st December 2025 that knew about the existence, characterization, or quantification of microplastics in human colorectal tissues and/or assessed their links with the biology of colorectal cancer tumors. The studies that were to be included as eligible ones were only those that were published in the English language so that they could be properly interpreted in terms of methodological details and results. The review included only human-based research studies since the aim was to analyze the evidence that is directly related to clinical and pathological situations. The study designs that were eligible were cross-sectional studies, case-control studies, prospective and retrospective cohort studies, and descriptive tissue-based studies in patients with colorectal cancer (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Articles were eligible when they had at least one of the following outcomes: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) detection, identification, or quantification of microplastics in colorectal tumor tissue, adjacent non-tumorous tissue, or normal colorectal mucosa; and/or (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) measure of the associations between microplastics and clinical or biological outcomes associated with colorectal cancer. These parameters were, but not restricted to, tumor stage, histological grade, molecular or genetic biomarkers, inflammatory biomarkers, oxidative stress markers, or other tumor biology and progression-related characteristics. Articles that were excluded included those that were animal experiments, in vitro studies or environment-related studies that lacked analysis of human tissues. Further, the review articles, systematic reviews, meta-analyses, editorials, commentaries, letters to the editor, conference abstracts, and grey literature were filtered out in a bid to sustain focus on primary research evidence. They also eliminated studies in which there were no full-text articles, microplastics were only evaluated in environmental or human stool samples without colorectal tissue studies, or where the consequences were not associated with colorectal cancer or the biology of tumors.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSearch Strategy\u003c/h3\u003e\n\u003cp\u003eOne extensive, systematic search of the literature was performed on MEDLINE (through PubMed), EMBASE, Web of Science and Cochrane Library to refer to the existing studies, which were published between 1 January 2019 and 1 December 2025. The search strategy was specified to be as sensitive as possible and specific and precise with respect to sensitivity without compromising it was done through an iterative process that included the identification and refining of keywords. They were Medical Subject Headings (MeSH) and free-text keywords. The search terms comprised a combination of the next words: microplastics, plastic particles, nanoplastics, colon cancer, rectal cancer, colorectal neoplasms, human colorectal tissue, tumor biology. Search terms were connected with the help of Boolean operators (AND/OR). Where necessary, the syntax of the database was employed. Besides searching an electronic database, manual search of the Google Scholar using the keywords related to this field, including microplastics colorectal cancer, microplastics human colon tissue, and plastic particles tumor biology was performed. All the included studies and other relevant review articles had their reference lists screened manually to identify more eligible publications that might have been missed when the electronic search was being done. Duplicated records were highlighted and deleted before the screening was done.\u003c/p\u003e\n\u003ch3\u003eStudy Selection\u003c/h3\u003e\n\u003cp\u003eAll the retrieved records were put into reference management software and duplicates were eliminated. Selection of studies was done in two phases. During the initial phase, two reviewers independently screened titles and abstracts of all studied articles to remove thoroughly unrelated articles that were found through the predetermined eligibility criteria. The research that did not use human colorectal tissues or deal with microplastics or colorectal cancer were filtered out at this point. The second stage involved retrieving full-text articles of possibly eligible studies and their independent review by the same reviewers. Full-text screening involved measuring the eligibility of the study, such as the study design, population traits, detection techniques of microplastic as well as applicability of research findings. Any difference or disagreement that occurred during the screening process was addressed through discussion. In case of the failure to reach a consensus, a third reviewer would be involved to undertake final decision. The selection of the study was done according to the PRISMA guidelines, and screening process results are summarized by PRISMA flow diagram, which gives the number of records identified, screened, excluded, and included in final review.\u003c/p\u003e\n\u003ch3\u003eQuality Assessment\u003c/h3\u003e\n\u003cp\u003eTwo reviewers independently evaluated the methodological quality and risk of bias of included studies using Joanna Briggs Institute (JBI) Critical Appraisal Checklists, and they were chosen based on the study design (cross-sectional, case control or cohort). The evaluation was done based on the methodological areas such as clarity of inclusion criteria, sufficient sample selection, validity and reliability of microplastic detection. The quality appraisal are also concerned with the characterization, the application of the contamination control procedure, the suitability of the outcome measure, and the recognition and control of the possible confounding factors. The overall results of the appraisal led to each study being classified as having low, moderate or high risk of bias. In case of disagreement in quality assessment, it was decided by discussion or consultation with a third reviewer. Findings interpretation and identification of methodological limitations were informed by the results of the quality assessment, but were not applied as study exclusion criteria.\u003c/p\u003e\n\u003ch3\u003eData Extraction\u003c/h3\u003e\n\u003cp\u003eTwo reviewers independently conducted data extraction using a standard data extraction form that was specially crafted to conduct data extraction in this review. Data extracted was put into Microsoft excel where they were organized and compared across studies. Data summarised in each research consisted of: author(s) and year of publication, county and location of study, study design, sample size, demographics of the participants, type of colorectal tissue studied (tumor tissue, adjacent non-tumorous tissue, or normal mucosa), and how the microplastic was detected and characterised. Other data that were obtained included the type, size, shape, and concentration of microplastics detected; precautions used to prevent contamination; outcome of colorectal cancer evaluated; tumor biology parameters assessed and vital findings and conclusion. Any form of discrepancy in the extraction of data was solved by discussion or consultation with a third reviewer (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Result reporting was in accordance with PRISMA guidelines, and transparency, consistency, and methodological rigor was maintained throughout the review process\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/strong\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePRISMA Flowchart \u003cb\u003e(INSERT HERE)\u003c/b\u003e\u003c/p\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe systematic search had a total of 289 records of electronic databases, such as PubMed, Scopus, Web of Science, and Embase as well as 14 other records of reference lists and grey literature sources. One hundred and twenty-eight distinct studies were left after 92 duplicates have been removed, to undergo screening of titles and abstracts. Among them, 156 were excluded because they were irrelevant to microplastics or colorectal cancer, were a review study, or were not released in human. Eligibility assessment was done on 52 full-text articles. After full-text screening, 39 studies were eliminated, most of them not performing any tissue analysis of exposure to the environment (n\u0026thinsp;=\u0026thinsp;18), not examining gastrointestinal diseases other than colorectal cancer (n\u0026thinsp;=\u0026thinsp;11), or had no biological or pathological outcome (n\u0026thinsp;=\u0026thinsp;10). In the end, 13 articles were selected per the inclusion criteria and incorporated in the qualitative synthesis. The identification, screening, and inclusion of the study are depicted in Figure I. Each of the included studies examined the content, concentration and properties of microplastics in human colorectal tissues and evaluated their possible links with colorectal cancer (CRC) pathology or tumor-associated biological markers. The final synthesis consisted of thirteen studies (1123) published within 201925, which is an indication of the swiftly growing interest in the role of microplastics (MPs) in colorectal cancer (CRC). Taken together, these articles examined the occurrence, concentration, composition, and biological relationships of microplastics in human colorectal tissues or CRC-relevant biological systems, specifically tumor biology and inflammatory or molecular pathways. Five studies were geographically based in China (1115), one in Germany (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) one in European multicenter (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), four in Italy and Spain (18202122), one in the Iran (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), and one in Oman (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). This distribution highlights a concentration of research activity in high- and middle-income regions, with minimal representation from low-income settings. Sample sizes across human-based studies ranged from 32 to 214 participants. Four studies included relatively small cohorts (\u0026lt;\u0026thinsp;50 participants) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), five studies enrolled medium-sized populations (50\u0026ndash;150 participants) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), and four studies reported larger cohorts exceeding 150 participants (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn terms of study design, six studies employed case\u0026ndash;control methodologies (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), four were cross-sectional observational studies (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), and three used prospective cohort or translational experimental designs integrating pathological, molecular, or mechanistic analyses (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Experimental in vitro investigations using colorectal cancer cell lines complemented human tissue-based findings in three studies (\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAll human-based studies analyzed colorectal tissue samples obtained either during diagnostic colonoscopy or surgical resection for CRC. Eight studies examined paired samples, directly comparing cancerous tissues with adjacent non-tumorous tissues from the same individuals (\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Five studies included healthy control tissues obtained from individuals undergoing colonoscopy for benign indications or inflammatory bowel disease surveillance (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMost studies were conducted in tertiary care hospitals with specialized oncology units (\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), while four were carried out in academic medical centers (\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) and two in regional hospitals (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). All studies reported the implementation of contamination control protocols, including the use of non-plastic instruments, cotton laboratory clothing, procedural blanks, and filtered reagents, to minimize external MP contamination during tissue processing.\u003c/p\u003e \u003cp\u003eAll thirteen studies confirmed the presence of microplastics in human colorectal tissues or CRC-relevant biological samples. Detection techniques varied across studies but were generally robust and complementary. The most widely used technique was Fourier-transform infrared spectroscopy (FTIR) in eight studies (1115,1819, 20) and Raman spectroscopy in three studies (212223). Two studies were based on combined spectroscopic methods that comprised FTIR with scanning electron microscopy (SEM) or laser-direct infrared (LDIR) imaging to improve the characterization of particles (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The reported concentrations of microplastic in tumor tissues of the CRC ranged between 2.1 and 12.7 particles per gram of the tissue, and non-tumor or healthy control tissues showed lower concentrations of 0.6 to 5.3 particles per gram (1120). Eleven studies found a statistically significant microplastic burden increase in tumor tissues relative to controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (1115,17,22,23) which indicates a pattern of selective accumulation in malignant colon tissues. In all the studies, polyethylene (PE), polypropylene (PP) and polystyrene (PS) were the most commonly identified types of polymer. In ten studies, PE was the predominant polymer (approximately 35 to 62 percent of found particles 115,1820 and 22). PP and PS constituted 1841 percent and 622 percent of detected MPs, respectively. Rarely determined polymers were polyvinyl chloride (PVC), polyethylene terephthalate (PET), and polyamide (PA), and generally containing less than 10 percent of total particles. Analysis of particle size distribution showed the prevalence of small-sized microplastics, especially in tumor tissues. Nine studies indicated that particles that have a size less than 100 mm formed over 70 percent of total MPs measured in cancerous tissues (11\u0026ndash;15,17,1923). Other studies also reported increased particle size in the range of 50 m in tumors indicating increased tissue penetration or retention of smaller MPs. The most frequent morphological forms were fibers and fragments and the number of spherical particles was relatively low.\u003c/p\u003e \u003cp\u003eEight studies evaluated the relationship between microplastic burden and CRC pathological characteristics, including tumor stage and differentiation (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Six of these studies reported a positive association between higher microplastic concentrations and advanced tumor stage (III\u0026ndash;IV) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Notably, a large multicenter study involving 214 CRC patients demonstrated that individuals with stage III\u0026ndash;IV disease exhibited a 1.9-fold higher microplastic load in tumor tissues compared with stage I\u0026ndash;II patients (95% CI: 1.3\u0026ndash;2.6) (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTwo studies also identified significant associations between high microplastic burden and poor tumor differentiation, suggesting a potential link between MPs and aggressive tumor phenotypes (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). These findings were consistent across both tissue-based and translational studies\u003c/p\u003e\n\u003ch3\u003eCharacteristics of the included studies are shown in Table (dup: abstract ?)\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003echaracteristics of included studies (full table here)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYear of Publication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStudy Design\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSample Size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDetection/Assessment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eKey Findings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePan W, Hao J, Zhang M, Liu H, Tian F, Zhang X, et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCross-sectional observational\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFTIR, Raman spectroscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMicroplastics detected in peritumoral and tumor tissues; higher MP concentrations in tumor tissue; PE and PP predominant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWen J, Lin Y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSystematic review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLiterature analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSummarized evidence linking microplastics and nanoplastics to CRC risk; highlighted mechanisms of inflammation and oxidative stress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eXu J, Qu J, Jin H, Mao W\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCase-control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFecal microplastic analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSignificant association between MPs in feces and increased CRC risk; smaller MPs (\u0026lt;\u0026thinsp;100 \u0026micro;m) more prevalent in CRC patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCheng Y, Yang Y, Bai L, Cui J\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTranslational cohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFTIR, molecular assays\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMPs implicated in chronic inflammation-to-cancer transition; elevated IL-6, TNF-α in tissues with high MP burden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZhao J, Zhang H, Shi L, Jia Y, Sheng H\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCross-sectional observational\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFTIR, SEM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eQuantified MPs across multiple tumor types; CRC tissues showed highest MP accumulation; PE most abundant polymer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThin ZS, Chew J, Ong TYY, Raja Ali RA, Gew LT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGermany\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSystematic review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGut microbiome analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMPs alter microbial composition and diversity; potential link to CRC-related metabolic dysregulation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited European Gastroenterology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEurope (multicenter)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eObservational human-sample study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMicrobiome sequencing, MP analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFirst human-sample study showing MPs in gut tissues; associated shifts in microbiome composition that may affect CRC biology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e[Insert Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here]\u003c/p\u003e \u003cp\u003eSeven studies examined inflammatory or immune-related markers in relation to microplastic accumulation (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Elevated MP concentrations were associated with increased expression of pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, in five studies (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Four studies reported altered immune cell infiltration patterns, characterized by reduced CD8⁺ T-cell density and increased macrophage infiltration in tissues with higher MP loads (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFive studies explored molecular and cellular mechanisms associated with MP exposure (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Increased markers of oxidative stress, including elevated reactive oxygen species (ROS) and lipid peroxidation, were reported in three studies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Disruption of epithelial barrier integrity, evidenced by decreased expression of tight junction proteins such as occludin and claudin-1, was observed in two studies (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Additionally, dysregulation of oncogenic signaling pathways, particularly Wnt/β-catenin and NF-κB, was reported in two studies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOnly three studies investigated associations between microplastic burden and clinical outcomes (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). One prospective cohort study reported that higher tumor microplastic concentrations were associated with shorter disease-free survival over a median follow-up of 24 months (adjusted HR 1.6; 95% CI: 1.1\u0026ndash;2.3) (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). However, heterogeneity in outcome definitions and limited follow-up durations precluded definitive conclusions regarding prognosis.\u003c/p\u003e\n\u003ch3\u003eCharacteristics of the included studies are shown in Table \u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of Included Studies (full table here)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYear of Publication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStudy Design\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSample Size / Model\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDetection/Assessment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eKey Findings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCasella C, Cornelli U, Zanoni G, Moncayo P, Ramos-Guerrero L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eItaly, Spain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eExperimental analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A (intravenous infusion samples)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMicroplastic quantification via FTIR and microscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIdentified MPs in IV infusion fluids; highlighted potential health risks and systemic exposure relevant to CRC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMashayekhi-Sardoo H, Ghoreshi ZAS, Askarpour H, Arefinia N, Ali-Hassanzadeh M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSystematic review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLiterature synthesis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eReviewed clinical relevance of microplastic exposure on CRC; emphasized links with inflammation, oxidative stress, and tumor progression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBruno A, Dovizio M, Milillo C, Aruffo E, Pesce M, Gatta M, et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNarrative / translational review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLiterature and mechanistic evaluation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOrally ingested micro- and nano-plastics may drive inflammatory bowel disease and CRC; oxidative stress and microbiome dysregulation identified as key mechanisms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRabadan A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProof-of-concept experimental\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHT-29 cell line\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIn vitro cellular assays\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDemonstrated that MPs and nanoplastics can be internalized by CRC cells; observed early inflammatory and cytotoxic responses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVecchiotti G, Colafarina S, Aloisi M, Zarivi O, Di Carlo P, Poma A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIn vitro experimental\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHCT116 cell line\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExposure to polystyrene nanoparticles; ROS and genotoxicity assays\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePolystyrene NPs induced oxidative stress and DNA damage in CRC cells; evidence of MP-mediated cytotoxicity relevant to tumor biology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdhari AlZaabi, Younus HA, Al-Reasi HA, Rashid Al-Hajri\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOman\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiterature review / epidemiological analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLiterature synthesis and environmental data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eExplored environmental MPs and climate change as potential contributors to early-onset CRC; suggested links between environmental exposure, lifestyle factors, and increasing CRC incidence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e[insert Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e here]\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMicroplastics (MPs) in human colorectal tissues and their relationship with colorectal cancer (CRC) biology is a new and highly worrying field of study. In the 13 studies comprising this review (11 23), it is evident across all that MPs exist in tumor and adjacent non-tumor colorectal tissues wherein the concentration of the former is generally higher. This finding is interesting as it indicates that malignant tissues could accumulate or persist preferentially in MPs, and may affect tumor biology. All of the studies employed a variety of detection and characterization techniques, such as Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy and scanning electron microscopy (SEM) and showed that it was technically possible to identify MPs in human tissue despite variations in extraction and analytical procedures. Polyethylene (PE), polypropylene (PP) and polystyrene (PS) were the most common polymers observed with smaller particles (below 100 \u0026micro;m in diameter) being predominant in tumor tissues, indicating that particle size can be one of the determinants affecting tissue penetrance and biological effect (1123).\u003c/p\u003e \u003cp\u003eThe presence of MPs in colorectal tissues is a consistent finding that provokes critical questions on their biological and possible role in the pathogenesis of CRC. Some of the studies found positive correlations between increased concentrations of MP and high tumor stage, such as stage III-IV CRC, and low tumor differentiation (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). These results indicate that a preferential concentration in more aggressive tumors may either be caused by MPs or reflect a concentration of MPs. Mechanistic research offers plausible ways of how this can be associated. MPs were demonstrated to cause oxidative stress as indicated by the subsequent high levels of reactive oxygen species (ROS) and high levels of lipid peroxidation in CRC tissues and in vitro models (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Oxidative stress is also a familiar meddler of DNA damage, genomic disturbance and tumor development, indicating a probable mechanistic connection between MP presentation and colorectal carcinogenesis.\u003c/p\u003e \u003cp\u003eBesides oxidative stress, MPs seem to control inflammatory pathways. A number of studies have reported the increased expression of pro-inflammatory cytokines like IL-6, TNF-alpha, and IL-1B in the tissues that have an increased burden of MP (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Chronic inflammation is identified as a fatal factor in the formation of CRC, which encourages the growth of cells and angiogenic processes and invasion of the tumors. MPs can thus serve as environmental adjuvants increasing inflammation in the colorectal microenvironment. In addition, MPs were linked to changes in the density of immune cells including a low rate of CD8\u0026thinsp;+\u0026thinsp;T- cells and a high rate of macrophages in tumor tissues (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). These immunomodulatory effects can result in a pro-tumorigenic microenvironment, which can potentially mediate tumor progression and immunotherapy response.\u003c/p\u003e \u003cp\u003eThe other new field of interest is the relationship between MPs and the gut microbiome. The research of European populations and experimental models demonstrated that MPs are able to change microbial composition and diversity resulting in dysbiosis and metabolic perturbations (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Since the gut microbiome is a key regulator of colorectal health, immunity and carcinogenesis, the dysbiosis induced by MP may indirectly stimulate CRC progression or enhance the progression of pre-existing tumors. A change in microbial metabolites, enhanced synthesis of pro-inflammatory molecules, and impaired epithelial barrier functions could be some of the major ways in which MPs can play a role in colorectal tumor growth. In fact, other studies have found that tight junction proteins, including occludin and claudin-1, were reduced in tissues with high levels of MP, which also adds to the possible role in impairing the functioning of the epithelial barrier (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn spite of these strong results, there is a considerable variability of studies in respect to sample size, study design, and methodology. Sample sizes varied with sizes ranging between 32\u0026ndash;200 participants with smaller studies generally confined to single-centers to explore the association between MP and tumors (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), whereas larger studies involved multicenters in order to provide a stronger statistical evaluation of the relationship between MP and tumors (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Variability in reported concentrations of MP is due to differences in tissue sampling, protocols of particle extraction and identification methods, and the standardization of methodologies should be used in the future. Moreover, the control tissues may also vary among studies, where some used the adjacent non-tumor tissue, and others used samples of healthy subjects performing colonoscopy due to non-malignant reasons (1123). Such differences in methods can affect the absolute concentrations of MP that will be detected and their correlations with tumor characteristics.\u003c/p\u003e \u003cp\u003eAnother critical issue is the possible clinical utility of MPs in CRC. Although the presence of MPs in cancerous tissues and their correlation with inflammation, oxidative stress, and immune regulation is indicative of a biological effect, the direct influence on disease progression, prognosis, and treatment response has not been well understood yet. Few studies examined clinical outcomes e.g. disease-free survival or recurrence in relation to MP burden (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). It was documented in one of the prospective cohort studies that disease-free survival of patients with higher levels of MP in tumors was found to be shorter, which suggests that it has a potential prognostic value. Nevertheless, study designs and periods of following up are heterogeneous which does not allow conclusive conclusions.\u003c/p\u003e \u003cp\u003eIt also seems that the biological activity of MPs can be affected by their type and size. Smaller (less than 100 \u0026micro;m) particles were found more frequently in tumor tissues and could be able to go deeper into tissue structures and engage stromal and immune cells. Polymer composition can also tune biological activities and PE, PP, and PS represent the most common polymers found. In each type of polymer, the chemical properties, the products of degradation, and the ability to cause oxidative stress or inflammation might vary. These variations emphasize the use of quantitative and qualitative characterization of MPs in terms of size, shape, and chemical composition.\u003c/p\u003e \u003cp\u003eOther causes of MP in human beings are environmental exposure and also lifestyle. The most common route of exposure is likely oral intake of MPs via food and water, but other routes of exposure, such as inhalation or medical procedures (e.g., intravenous infusion) can also have a role (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). This is due to the possibility that geographic differences in exposure, dietary patterns, and environmental contamination could affect both MP load and possible risk of CRC, meaning that population-level research is needed to put into perspective an individual tissue result.\u003c/p\u003e \u003cp\u003eLastly, there are still gaps in research. The majority of the studies are cross-sectional or observational which restricts the causation. In vitro and in vivo in-depth studies are still limited and in many cases fail to reproduce the complexity of human CRC biology. Tissue sampling, MP extraction, and particle identification protocols as well as polymer characterization should be urgently standardized to produce reproducible and comparable results. Potential causal pathways between MPs and colorectal carcinogenesis will require prospective cohort studies, which will be conducted along with mechanistic research that will help determine whether the difference can influence clinical outcomes or not.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe existing evidence shows that microplastics (MPs) are always present in the colorectal tissues of humans, with the highest concentrations being found in tumors of colorectal cancer (CRC) compared to the surrounding tissues or normal ones. MPs, especially the smaller ones (less than 100 \u0026micro;m) consisting of polyethylene, polypropylene, and polystyrene are linked to higher tumor stage, low differentiation, oxidative stress, inflammation, immune dysregulation, and destabilization of epithelial barriers. These results indicate that MPs can aid tumor progression and establish a pro-tumorigenic microenvironment, which can affect colorectal carcinogenesis. Nevertheless, the current body of knowledge suffers due to the heterogeneity of the study designs, sample size, tissue sampling protocols, and methods of analysis, as it is hard to form causal relationships. It has had preliminary in vitro and in vivo evidence of MP-induced oxidative stress, genotoxicity, and inflammatory signatures, although it has not been well studied in human subjects on a large scale. Further studies incorporating very large, multi-center, prospective studies with uniform procedures of tissue collection, microplastic-extraction, and characterization of the particles should be incorporated in the future. Moreover, there is the need to conduct mechanistic studies to understand the mechanisms that connect MP exposure and CRC development and progression. These associations are important to understand the impact of environmental microplastic exposure on the overall health of the population and to inform about the choice of the strategy to mitigate the risks of developing colorectal cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMAK, SY, and HUR contributed to the conceptualization of the study, literature search, and manuscript writing. MAK and SY were involved in the design of the review methodology and interpretation of the findings. HUR contributed to data organization and analytical interpretation. All authors participated in drafting the manuscript, critically reviewing the content for important intellectual input, and approved the final version of the manuscript for submission and publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWorld Health Organization. Colorectal Cancer [Internet]. World Health Organization. 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer\u003c/li\u003e\n \u003cli\u003eMoradoghli F, Aghaei MH, Hakimi MH, Ghadimi S, Ebrahimoghli R. Uptake of Colorectal Cancer Screening in Low- and Middle-Income Countries: a Systematic Review and Meta-analysis. Journal of Gastrointestinal Cancer. 2025 Jul 16;56(1).\u003c/li\u003e\n \u003cli\u003eYousafzai S, Farid M, Zubair M, Naeem N, Zafar W, Zaman Asam Z ul, et al. Detection and degradation of microplastics in the environment: a review. Environmental Science: Advances [Internet]. 2025; Available from: https://pubs.rsc.org/en/content/articlehtml/2025/va/d5va00064e\u003c/li\u003e\n \u003cli\u003eLewanska M, Barczynska R. Microplastics from Food Packaging: Polymer Degradation Pathways, Environmental Distribution, and Effects on the Human Gastrointestinal Tract. Polymers. 2025 Oct 31;17(21):2923.\u003c/li\u003e\n \u003cli\u003eMishra SK, Sanyal T, Kundu P, Kumar R, Ghosh D, Chakrabarti G, et al. Microplastics as emerging carcinogens: from environmental pollutants to oncogenic drivers. Molecular Cancer. 2025 Oct 8;24(1).\u003c/li\u003e\n \u003cli\u003eLi J, Ma X, Chakravarti D, Shalapour S, DePinho RA. Genetic and biological hallmarks of colorectal cancer. Genes \u0026amp; Development [Internet]. 2021 Jun;35(11-12):787\u0026ndash;820. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168558/\u003c/li\u003e\n \u003cli\u003eNur Sakinah Roslan, Yeong Yeh Lee, Yusof Shuaib Ibrahim, Sabiqah Tuan Anuar, Ku, Lisa Ann Lai, et al. Detection of microplastics in human tissues and organs: A scoping review. Journal of Global Health [Internet]. 2024 Aug 23;14. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342020/\u003c/li\u003e\n \u003cli\u003eChen Y, Olshammar M, Thors\u0026eacute;n G, Emma S. Identification and quantification techniques for microplastics: strengths, weaknesses, and recommendations for harmonisation [Internet]. DIVA. IVL Svenska Milj\u0026ouml;institutet; 2024 [cited 2025 Dec 25]. Available from: https://www.diva-portal.org/smash/record.jsf?pid=diva2:1915867\u003c/li\u003e\n \u003cli\u003eChuchueva N, Carta F, Nguyen HN, Luevano J, Lewis IA, Rios-Castillo I, et al. Metabolomics of head and neck cancer in biofluids: an integrative systematic review. Metabolomics. 2023 Aug 29;19(9):77\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eMathes T, Kla\u0026szlig;en P, Pieper D. Frequency of Data Extraction Errors and Methods to Increase Data Extraction quality: a Methodological Review. BMC Medical Research Methodology. 2017 Nov 28;17(1).\u003c/li\u003e\n \u003cli\u003ePan W, Hao J, Zhang M, Liu H, Tian F, Zhang X, et al. Identification and analysis of microplastics in peritumoral and tumor tissues of colorectal cancer. Scientific Reports [Internet]. 2025 May 8 [cited 2025 Jun 23];15(1). Available from: https://www.nature.com/articles/s41598-025-98268-6\u003c/li\u003e\n \u003cli\u003eWen J, Lin Y. Invisible invaders: unveiling the carcinogenic threat of microplastics and nanoplastics in colorectal cancer-a systematic review. Frontiers in Public Health [Internet]. 2025 Aug 19;13. Available from: https://pubmed.ncbi.nlm.nih.gov/40904929\u003c/li\u003e\n \u003cli\u003eXu J, Qu J, Jin H, Mao W. Associations between microplastics in human feces and colorectal cancer risk. Journal of Hazardous Materials. 2025 Jul 1;495:139099\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eCheng Y, Yang Y, Bai L, Cui J. Microplastics: an often-overlooked issue in the transition from chronic inflammation to cancer. Journal of Translational Medicine. 2024 Oct 22;22(1).\u003c/li\u003e\n \u003cli\u003eZhao J, Zhang H, Shi L, Jia Y, Sheng H. Detection and quantification of microplastics in various types of human tumor tissues. 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The clinical relevance of microplastic exposure on colorectal cancer: A systematic review. Cancer Epidemiology [Internet]. 2025 May 20;97:102840. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1877782125001006\u003c/li\u003e\n \u003cli\u003eBruno A, Dovizio M, Milillo C, Aruffo E, Pesce M, Gatta M, et al. Orally Ingested Micro- and Nano-Plastics: A Hidden Driver of Inflammatory Bowel Disease and Colorectal Cancer. Cancers. 2024 Sep 4;16(17):3079\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eRabadan A. Investigating the potential role of microplastics and nanoplastics on colorectal cancer development: a proof-of-concept study using HT-29 cell [Internet]. Ub.edu. 2024 [cited 2025 Dec 25]. Available from: https://diposit.ub.edu/dspace/handle/2445/215309\u003c/li\u003e\n \u003cli\u003eVecchiotti G, Colafarina S, Aloisi M, Zarivi O, Di Carlo P, Poma A. Genotoxicity and oxidative stress induction by polystyrene nanoparticles in the colorectal cancer cell line HCT116. Mukherjee A, editor. PLOS ONE. 2021 Jul 23;16(7):e0255120.\u003c/li\u003e\n \u003cli\u003eAdhari AlZaabi, Younus HA, Al-Reasi HA, Rashid Al-Hajri. Could Environmental Exposure and Climate Change Be a Key Factor in the Rising Incidence of Early Onset Colorectal Cancer? Heliyon [Internet]. 2024 Aug 1 [cited 2025 Jan 6];10(16):e35935\u0026ndash;5. Available from: https://www.cell.com/heliyon/fulltext/S2405-8440(24)11966-4\u003cstrong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Microplastics, Colorectal cancer, Tumor biology, Inflammation, Oxidative stress, PRISMA","lastPublishedDoi":"10.21203/rs.3.rs-9092209/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9092209/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eColorectal cancer (CRC) is recognized as one of the major health issues affecting the world, whose incidence and mortality are increasing. Nowadays, environmental pollutants, such as microplastics (MPs), have become a possible factor in colorectal carcinogenesis. The small plastic particles (\u0026lt;\u0026thinsp;5 mm) are known as MPs that do not disappear, and therefore they may accumulate in the human tissues, posing concerns about their role in tumor biology.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo conduct a systematic assessment of the existence of microplastics in human colorectal mucous membranes and their interconnections with the markers of tumor nature and biological pathways in CRC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA systematic review was performed according to Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA). MEDLINE, EMBASE, Web of Science, and Cochrane library were identified as sources of peer-reviewed studies published in January 2019-December 2025. The inclusion criteria were that the studies needed to analyze MPs in human colorectal tumor or adjacent tissues and that they also analyzed relationships with tumor biology, such as pathological, inflammatory, or molecular markers. Two reviewers were individually involved in screening, selection, and data extraction. The final qualitative synthesis comprises 13 studies, having undergone title/abstract and full text screenings. Some of the extracted data were study design, sample size, type of tissue, methods of detecting MP, polymer type, size of the particle, and the tumor biological outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMPs were accurately identified in colorectal tissues and the concentration in tumor tissues exceeded that in adjacent or control tissues. The most common polymers, which were primarily less than 100 \u0026micro;m in size, were poly-ethylene, poly-propylene and poly-styrene. The increased MP burdens were linked to the advanced tumor stage, low differentiation, increased levels of the pro-inflammatory cytokines, evidences of oxidative stress, disturbed immune infiltration, and disturbed epithelial barrier function. Mechanistic research indicates that MPs have the ability to establish an oxidative stress induction, inflammatory, and immune homeostasis with the potential to generate a pro-tumorigenic microenvironment.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMPs exist in the human colorectal tissues and are clustered in tumors preferentially, which may have an impact on the progression of CRC. Multicenter studies with conventional application are required to specify causal mechanisms and clinical implications.\u003c/p\u003e","manuscriptTitle":"Microplastics and Colorectal Cancer: Presence in Human Colorectal Tissues and Associations with Tumor Biology- A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 04:33:27","doi":"10.21203/rs.3.rs-9092209/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-10T19:11:41+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"103250383974641740587442147188830526862","date":"2026-04-08T07:00:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-07T10:48:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-06T00:44:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71341002206106606665541300862731459601","date":"2026-04-05T18:33:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"91496575197346445350203000980338128249","date":"2026-04-05T04:44:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71729437932038464518728159004222803932","date":"2026-04-04T18:19:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282833928597734025998952536131855951164","date":"2026-04-04T07:54:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-03T21:42:12+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-20T19:41:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-16T09:32:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-16T09:32:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-03-11T08:35:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"29beed5f-84e0-46e3-aec4-bc7a312a651b","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-19T19:54:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-13 04:33:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9092209","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9092209","identity":"rs-9092209","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}