Abstract
Objective
Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally, and researchers continue to explore its underlying factors. This systematic review and meta-analysis study aimed to clarify the prevalence and potential association between intestinal parasitic infections (IPIs) and CRC.
Methods
A comprehensive search was conducted across databases that contain articles in English, including PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar, to identify articles published up to October 2024 that reported on the prevalence of IPIs in CRC patients. Selected studies were screened according to inclusion and exclusion criteria. A random-effects model was used to estimate the pooled prevalence and odds ratios (ORs) for association IPIs in CRC.
Results
A total of 70 studies were included, and 46 case–control and cross-sectional studies were analyzed. The pooled prevalence of IPIs among CRC patients was determined to be 19.67% (95% CI: 14.81% to 25.02%). Furthermore, individuals with parasitic infections exhibited a significantly higher likelihood of developing CRC, with an OR of 3.61 (95% CI: 2.41—5.43).
Conclusion
This study demonstrated a significantly high prevalence of parasitic infections, including both helminths and protozoa, among patients with CRC. The analysis revealed a notable association between IPIs and CRC, suggesting that these infections may contribute to the development and progression of the cancer.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12876-025-04144-y.
Keywords: Colorectal cancer, Intestinal parasitic infection, Systematic review, Meta-analysis
Introduction
Colorectal cancer (CRC) is a major global health issue, ranking second among malignancies in terms of mortality, with approximately 9.2% of cases resulting in death [1]. Although there have been progresses in surgical methods, the adoption of screening and updated therapy guidelines [2], evidence suggests a concerning trend, with anticipated rises of 60% and 71.5% in mortality rates for rectal and colon cancer to the year 2035, respectively [3]. These statistics emphasize the urgent need for enhanced prevention, early detection, and effective treatment strategies to address the growing burden of CRC worldwide [1].
There are numerous environmental and biological risk factors contributing to the development of CRC, among them, infectious pathogens are increasingly recognized as potential contributors to CRC [4]. Research indicates that approximately 16% of cancers worldwide are attributable to infectious agents [5]. This connection is particularly evident in CRC, where various studies have explored how bacteria and viruses may influence the disease's onset and progression [5]. Viruses are implicated in CRC development via direct infection of cells and indirect modulation of the gut microbiome [6]. For example, human papillomavirus (HPV) and cytomegalovirus are viruses associated with colon cancer risk, while Fusobacterium nucleatum, Enterococcus faecalis, Escherichia coli, and Salmonella sp. are bacteria that have been implicated in CRC [6].
Intestinal parasite infections (IPIs), especially in developing countries, are associated with various gastrointestinal disorders and may contribute to the development of CRC [7]. IPIs, comprising protozoa such as Cryptosporidium spp., Blastocystis spp., and Entamoeba histolytica, as well as helminths like Schistosoma spp., can provoke chronic inflammation and immunological dysregulation [8]. Previous researches suggested that immunopathological responses to parasitic infections may promote conditions favorable for cancer development [8]. Particularly, chronic inflammation plays a crucial role in triggering multiple cancers, including CRC [9]. Moreover, the inflammatory responses elicited by parasitic infections can promote carcinogenesis and contribute to the onset of CRC through different mechanisms including increasing oxidative stress that cause DNA damage, production of inflammatory cytokines such as IL-6, TNF-α, NF-κB which enhance cell proliferation, and modifications in the local microenvironment [7]. These connections underscore the intricate relationship between parasites and particular cancer types, accentuating the necessity of early detection, prevention, and efficacious treatments to mitigate long-term cancer risks linked to IPIs (6).
While epidemiological evidence suggests a potential relationship between IPIs and CRC, current evidence exhibits wide heterogeneity in findings. These variations are likely to reflect methodological variation among study design, population genetics, endemicity gradients, and methods of diagnosis. Additionally, the exact pathobiological pathways underlying this association are not yet elucidated. To address these knowledge gaps, we conducted a systematic review and meta-analysis to determine the prevalence of IPIs in CRC patients and to assess the association between these infections and CRC.
Methods and search strategy
Study design
This systematic review and meta-analysis was designed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure methodological rigor and transparency in reporting [10].
Search strategy
A comprehensive search was conducted using Medical Subject Headings (MeSH) combined with ("Colorectal Neoplasm"OR “Colorectal"OR"CRC"OR"colon cancer") AND ("Parasitic Diseases"OR"parasite"OR"parasitic infection") AND ("Protozoan Infections"OR"protozoa") AND ("Helminthiasis"OR"helminth") keywords. We conducted a comprehensive literature review using PubMed, ScienceDirect, Web of Science, and Scopus databases, along with Google Scholar for supplementary verification, to identify global publications examining the prevalence and association between IPIs and CRC. The search included English-language articles published up to October 2024 by three researchers independently [MH, BB, and MB]. The references from the relevant papers were checked for other associated articles not indexed through the electronic databases that may have been missed. The search results from five databases were imported into the EndNote X20 library for management.
Inclusion and exclusion criteria
Following the removal of duplicate records, three researchers (MH, BB, and MB) conducted an independent review of the remaining records, applying pre-specified inclusion and exclusion criteria to identify eligible studies. Finally, the articles were assessed based on the following criteria: (1) cross-sectional or case–control studies about the prevalence and relationship between parasite infection and CRC, (2) case reports and experimental studies providing details on the parasitic infection and CRC, (3) published articles written in English, and (4) studies conducted and published up to October 2024. Studies were excluded if (1) studies were in other languages except English, (2) letters to the editor, (3) studies had insufficient information, and (4) studies presented only the final results without providing the raw data (Fig. 1).
Fig. 1.
PRISMA flowchart diagram for the selection process of eligible studies
In the next step, four independent researchers (MH, BB, MGh, and MB) carefully reviewed all titles and abstracts identified, along with the full texts considered to be relevant. Possible disagreements were resolved by discussion and consensus with another author (RS). Titles and abstracts obtained from the initial electronic search were carefully assessed for potential inclusion based on the study type (prevalence of IPIs in CRC patients). Full texts were assessed, and unrelated articles were excluded. All articles that met the eligibility criteria were selected for the meta-analysis. Next, the desired data were extracted using a standardized data extraction form including the first author’s surname, the publication year, continent, countries, the types of methods used, the type of parasite, the type of cancer, total sample sizes, and the number of positive samples.
Study quality assessment
The quality of the included studies was evaluated using the Newcastle–Ottawa Scale (NOS) for case–control and cross-sectional studies. This quality assessment evaluates studies based on three main categories: selection, comparability, and exposure. Studies were rated as low, moderate, or high quality based on their scores. The NOS quality assessment assigned scores ranging from 0 to 9, with low quality defined as less than 3, moderate quality as 4 to 6, and high quality as 7 to 9.
Data analysis
In the current study, the StatsDirect statistical software package version 2.6.1 was used for data meta-analysis. Cochrane’s Q and the inverse variance (I2) statistics were employed to estimate the effects of probable factors in the heterogeneity of studies. If I2 was > 50% or > 75% and the P-value was < 0.01, the articles were considered to be heterogeneous or highly heterogeneous, respectively. If I2 was below 25%, the articles were considered homogeneous. Random- or fixed-effect models were used in case of significant or lack of heterogeneity to estimate the pooled prevalence and odds ratios (ORs) for association IPIs in CRC. In the last step, a funnel plot based on Egger’s test was used to calculate the possibility of publication bias during the analysis.
Results
Study characteristics
Our preliminary search on five databases, including PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar, yielded 1205 articles, but 46 were excluded from the study due to duplication. After a primary screening based on the titles of the articles, 99 studies were extracted. In the next step, by screening the abstracts and based on the inclusion/exclusion criteria, 29 articles were excluded. Finally, 70 articles were included in the analysis with respect to the inclusion/exclusion criteria (Fig. 1).
In this systematic review, the included papers were published between 1980 and 2024.
The data were derived from a comprehensive analysis of 70 studies, which encompassed case–control, and cross-sectional studies (n = 46), case report (n = 15), and experimental studies (n = 9). These investigations were conducted across 26 distinct countries, including China, Egypt, Iran, Uzbekistan, Turkey, Malaysia, Poland, Iraq, Colombia, Saudi Arabia, United Arab Emirates, Spain, United States America, Tunisia, Lebanon, Brazil, United Kingdom, Laos, Philippines, Tanzania, Netherlands, Korea, Sudan, Mexico, Germany and Japan. Our Meta-analysis included 46 case–control and cross-sectional studies (68 data sets), categorized into three distinct times: 6 studies from 1980 to 2008, 24 studies from 2012 to 2020, and 16 studies from 2020 to 2024. Table 1 is a baseline table of studies included in the meta-analyses.
Table 1.
The base line table of included cross-sectional and case–control studies
| NO | Author (Ref) | Year | Country | Type of study | Parasite | Diagnostic methods | NO. case | NO. Positive case | NO. control | NO. Positive | NOS QA score* |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Seleem et al. [11] | 2024 | Egypt | Case–control |
Blastocystis spp. Cryptosporidium E. histolytica G. intestinalis Microsporidia E. coli Iodamoeba butchilli E. hartmani |
Microscopic | 100 |
Blastocystis spp. (37) Cryptosporidium (14) E. histolytica (6) G. intestinalis (6) Microsporidia (6) E. coli (4) Iodamoeba butchilli (1) E. hartmani (1) |
100 |
B. hominis (13) E. coli (5) E. histolytica (4) G. intestinalis (3) |
8 |
| 2 | Labania et al. [12] | 2023 | United Arab Emirates | Case–control | Blastocystis spp. | Microscopic and PCR |
52 (CRC = 15 COGT = 37) |
CRC (n = 9) COGT (n = 12) |
52 | 9 | 6 |
| 3 | Abd El-Latif et al. [13] | 2023 | Egypt | Case–control | Cryptosporidium spp. | Microscopic, ZIehl–Neelsen method (ZN), PCR, ELISA | 40 |
Ziehl–Neelsen (13) ELISA (17) PCR (19) |
60 |
Ziehl–Neelsen (2) ELISA (3) PCR (3) |
7 |
| 4 | Mona I Ali et al. [14] | 2023 | Egypt | Case–control | Cryptosporidium parvum | Microscopic, Immunochromatographic and nested PCR | 100 |
Microscopic (n = 7) Immunochromatographic (n = 7) nested PCR (n = 40) |
20 | 0 | 7 |
| 5 | Gezici et al. [15] | 2023 | Turkey | Case–control | Blastocystis spp. Cryptosporidium spp. Giardia. intestinalis Cyclospora. Cayetanensis | Microscopic | 100 |
Blastocystis spp. (7) Cryptosporidium spp. (4) Giardia. intestinalis (2) Cyclospora. Cayetanensis (1) |
100 | Blastocystis spp. (2) | 7 |
| 6 | Ali et al. [16] | 2022 | Egypt | Cross-sectional | Blastocystis spp. | Microscopic, Culture, and PCR | 100 | 52 | 100 | 42 | 8 |
| 7 | Chen et al. [17] | 2022 | China | Cross-sectional | Giardia intestinalis | Microscopic and PCR | 307 | 25 | 8 | ||
| 8 | Ghanadi et al. [18] | 2022 | Iran | Case–control | Cryptosporidium spp. | Microscopic, PCR, Histopathological tests, Immunochemical test | 87 | 37 | 87 | 11 | 8 |
| 9 | Haghighi et al. [19] | 2022 | Iran | Cross-sectional | Entamoeba histolytica | PCR and immunohistochemical staining (IHC) | 19 | 5 | 81 | 2 | 7 |
| 10 | Castro et al. [20] | 2022 | Colombia | Cross-sectional | Blastocystis spp. Giardia intestinalis, and commensal amoebas | Microscopic, Ziehl–Neelsen staining, PCR | 28 | Blastocystis spp. (24/80) Giardia intestinalis (2/80) and commensal amoebas (5/80) | 6 | ||
| 11 | Redondo et al. [21] | 2022 | Spain | Case–control | Microsporidia spp. | Real-time PCR and IFA | 87 | 36 | 25 | 0 | 8 |
| 12 | Zhang et al. [22] | 2022 | China | Case–control | Pentatrichomonas hominis | Nested PCR | 25 | 8 | 9 | 6 | |
| 13 | Mahmoudvand et al. [23] | 2021 | Iran | Case–control | Blastocystis spp. | Microscopic and PCR | 67 | 16 | 67 | 6 | 8 |
| 14 | Hawash et al. [24] | 2021 | Saudi Arabia | Case–control | Blastocystis spp. | Microscopic | 75 | 20 | 25 | 2 | 8 |
| 15 | Sulzyc Bielicka et al. [25] | 2021 | Poland | Case–control | Blastocystis spp. | Microscopic and PCR | 107 | 13 | 124 | 3 | 8 |
| 16 | Karabey et al. [26] | 2021 | Turkey | Cross-sectional | Cryptosporidium spp. | Ziehl–Neelsen staining, real-time PCR and ELISA | 94 |
Ziehl–Neelsen staining (n = 2) real-time PCR (n = 5) ELISA (n = 5) |
6 | ||
| 17 | Asghari et al. [27] | 2020 | Iran | Cross-sectional | Blastocystis spp. | Microscopic, culture, and PCR | 4 | 2 | 6 | ||
| 18 | Zhang et al. [28] | 2020 | China | Case–control | Cryptosporidium. | Nested PCR | 116 | 20 | 141 | 0 | 8 |
| 19 | Nasir et al. [29] | 2020 | Iraq | Case–control | Cryptosporidium spp. | Modified Ziehl–Neelsen and crypto-strip (Immunochromatographic Assay) | 31 | 3 | 65 | 2 | 7 |
| 20 | wang et al. [30] | 2020 | China | Cross-sectional | Schistosoma | HE-stained formalin-fixed paraffin-embedded | 351 | 137 | 6 | ||
| 21 | Majeed et al. [31] | 2019 | Iraq | Cross-sectional | Blastocystis spp. | Microscopic. Direct DNA sequencing | 116 | 15 | 6 | ||
| 22 | Esteghamati et al. [32] | 2019 | Iran | Cross-sectional | Blastocystis spp. | Microscopic, nested PCR and amplification of the 18S rRNA gene | 39 | 11 | 8 | ||
| 23 | Mahmoudvand et al. [33] | 2019 | Iran | Cross-sectional |
Cystoisospora belli Cyclospora cayetanensis |
Microscopic and Ziehl–Neelsen stain | 87 |
C. belli (5) C. cayetanensis (3) |
6 | ||
| 24 | Zhang et al. [34] | 2019 | China | Case–control | Pentatrichomonas hominis | Microscopic and nested PCR | 116 | 44 | 142 | 13 | 8 |
| 25 | Sulzyc Bielicka et al. [35] | 2018 | Poland | Case–control | Cryptosporidium spp. | Immunoenzymatic test, Antigen-EIA technique | 108 | 14 | 125 | 5 | 8 |
| 26 | Essid et al. [36] | 2018 | Tunisia | Cross-sectional | Cryptosporidium spp. | Modified Ziehl Neelsen stain and PCR | 15 | 5 | 5 | ||
| 27 | Toychiev et al. [37] | 2018 | Uzbekistan | Case–control |
Blastocystis spp. Entamoeba dispar Entamoeba coli Ascaris lumbricoides Giardia intestinalis Hymenolepis nana Enterobius vermicularis Chilomastix mesnili Iodamoeba butchilli |
Microscopic andZiehl–Neelsen staining | 200 |
Blastocystis spp. (160) Entamoeba dispar (2) Entamoeba coli (14) Ascaris lumbricoides (6) Giardia intestinalis (20) Hymenolepis nana (3) Enterobius vermicularis (6) Chilomastix mesnili (40) Iodamoeba butchilli (45) |
200 |
Blastocystis spp. (36) Entamoeba dispar (1) Entamoeba coli (38) Ascaris lumbricoides (4) Giardia intestinalis (32) Hymenolepis nana (4) Enterobius vermicularis (9) Chilomastix mesnili (6) Iodamoeba butchilli (12) |
9 |
| 28 | Dabbagh et al. [38] | 2017 | Iraq | Case–control | Blastocystis spp. | Microscopic and ELISA | 40 | 15 | 80 | 33 | 6 |
| 29 | Mohamed et al. [39] | 2017 | Saudi Arabia | Case–control | Blastocystis spp. | Microscopic, culture, and PCR | 74 | 22 | 80 | 12 | 8 |
| 30 | Osman et al. [40] | 2017 | Lebanon | Case–control | Cryptosporidium spp. | Histological examination and PCR | 93 | colon cancer (n = 72) stomach cancer (n = 21) | 125 | 9 | 8 |
| 31 | Zhang et al. [41] | 2017 | China | Cross-sectional |
Enterocytozoon bieneusi Blastocystis spp. |
PCR |
Blastocystis (27) Enterocytozoon bieneus (5) |
4 | 8 | ||
| 32 | Yersal et al. [42] | 2015 | Turkey | Cross-sectional | Blastocystis spp. | Microscopic, culture, and PCR | 66 | 5 | 6 | ||
| 33 | Feng et al. [43] | 2015 | China | Cross-sectional | Schistosoma | Microscopic, Clonoscopy | 60 | 26 | 6 | ||
| 34 | Kumarasamy et al. [44] | 2014 | Malaysia | Case–control | Blastocystis spp. | Microscopic, culture, and PCR | 204 | 43 | 221 | 22 | 8 |
| 35 | Sanad et al. [45], | 2014 | Saudi Arabia | Case–control | Cryptosporidium spp. | Microscopic | 20 | 14 | 42 | 8 | 7 |
| 36 | Abdelkareem et al. [46] | 2014 | Malaysia | Cross-sectional | Schistosoma mansoni | Microscopic, colonoscopy and histopathology | 93 | 27 | 5 | ||
| 37 | Liu et al. [47] | 2013 | China | Cross-sectional | Schistosoma | Colonoscopy and Pathological Examination | 179 | 32 | 5 | ||
| 38 | Chandramathi et al. [48] | 2012 | Malaysia | Cross-sectional | Blastocystis spp. | Microscopic and culture | 15 | 7 | 5 | ||
| 39 | Shebl et al. [49] | 2012 | United States | Cross-sectional | Cryptosporidium spp. | Microscopic | 320 | 7 | 6 | ||
| 40 | Sulzyc Bielicka et al. [50] | 2012 | Poland | Cross-sectional | Cryptosporidium spp. | Immunoenzymatic test | 87 | 11 | 6 | ||
| 41 | Machado et al. [51] | 2008 | Brazil | Case–control | Strongyloides stercoralis | Baermann and Lutz, IFA, ELISA | 33 |
parasitological methods: n = 3 Serological methods: n = 8 |
44 |
parasitological methods: n = 1 Serological methods: n = 2 |
7 |
| 42 | Sulzyc Bielicka et al. [52] | 2007 | Poland | Cross-sectional | Cryptosporidium spp. | Microscopic. Enzyme and immunoassay | 55 | 23 | 5 | ||
| 43 | Steer et al. [53] | 2007 | United Kingdom | Cross-sectional | Blastocystis spp. | Microscopic | 83 | 40 | 5 | ||
| 44 | Qiu et al. [54] | 2005 | China | Case–control | Schistosoma japonicum | Microscopic and Colonoscopy | 142 | 42 | 285 | 41 | 7 |
| 45 | Zhong Xu et al. [55] | 1984 | China | Case–control | Schistosoma japonicum | skin test and histopathologic examination | 252 | 21 | 252 | 11 | 6 |
| 46 | Ming-Chai et al. [56] | 1980 | China | Cross-sectional | Schistosoma | histopathologic and H&E stain | 454 | 289 | 6 |
*High quality (7–9), moderate quality (4–6), and low quality (≤ 3) in case–control studies and high quality (6 and 7), moderate quality (3–5), and low quality (1 and 2) in cross sectional studies
Pooled prevalence of IPIs among CRC patients
The meta-analysis demonstrated high heterogeneity across the studies that were included in the analysis (Q = 2,191.58, I2 = 96.9%, P < 0.001). Since the heterogeneity was significant, the random effect was used to obtain the pooled prevalence of IPIs among CRC patients globally. Furthermore, the funnel plot and bias coefficient diagram indicated no evidence of publication bias (Harbord: bias = 3.33, Egger: bias = 6.14, P = 0.132). In general, the pooled prevalence of IPIs among the subjects studied in the world using the random effect method was 19.67% (95% CI = 14.81% to 25.02%) (Fig. 2). A total of 5,686 cases were examined in the study, among which 1,081 were identified as positive.
Fig. 2.
A meta-analysis of the pooled prevalence of IPI among cancer patients using random effects analysis
Results of the subgroup analyses
Using a random-effects model, the pooled prevalence of helminthic and protozoan infections in the studied populations worldwide was calculated to be 20.79% (95% CI: 8.35% to 36.96%) and 19.4% (95% CI: 14.39% to 24.96%), respectively.
Based on Table 2, Schistosoma spp. had the highest pooled prevalence in CRC patients, which pooled prevalence is 31.87% (95% CI: 16.33%−49.84%) with a pooled OR of 3.04 (95% CI: 1.62% to 5.71%). Furthermore, among protozoan infections, Blastocystis spp. and Cryptosporidium spp. had the highest pooled prevalence in CRC patients. The subgroup analysis based on different diagnostic methods revealed that the highest pooled prevalence of IPIs in CRC patients was identified using molecular methods, specifically PCR, with a prevalence of 28.34% (95% CI: 20.43%—36.99%). Furthermore, the parasitological method, microscopy, revealed pooled prevalence rates of 15.04% (95% CI: 9.30%—21.88%). Moreover, the highest pooled prevalence of IPIs among CRC patients was observed in years < 2010, which is 34.95% (95% CI: 14.28%—59.16%).
Table 2.
The Pooled prevalence of protozoan and helminthic infection among CRC patients and pooled prevalence of IPI in CRC patients in different subgroups
| Variables | No. study (datasets) | Positivity percent | Heterogeneity | Publication bias | ||||
|---|---|---|---|---|---|---|---|---|
| Pooled prevalence | CI 95% | Q | I2 | P-value | Egger | P value | ||
| Infection | ||||||||
| Protozoan | 39 (58) | 19.4% | 14.39%−24–96% | 1,431.44 | 96.1% | P < 0.0001 | 6.22 | P < 0.0001 |
| Helminthic | 9 (10) | 20.79% | 8.35%- 36.96% | 702.16 | 98.6% | P < 0.0001 | 10.32 | P = 0.05 |
| Parasite | ||||||||
| Cryptosporidium | 15 (15) | 26.75% | 15.21%−40.19% | 384.74 | 96.4% | P < 0.0001 | 6.30 | P = 0.001 |
| Blastocystis spp. | 19 (19) | 30.62% | 20.24%−42.10% | 388.69 | 95.4% | P < 0.0001 | 1.95 | P = 0.537 |
| Schistosoma | 7 (7) | 31.87% | 16.33%−49.84% | 301.90 | 98% | P < 0.0001 | 3.95 | P = 0.67 |
| Pantatrichomonas | 2 (2) | 37.05% | 29.32%−45.14% | 0.26 | 0% | P = 0.6081 | ||
| Microspora | 2 (2) | 19.36% | 0.00%−64.57% | 44.44 | 97.8% | P = 0.6081 | ||
| Iodamoeba | 2 (2) | 9.29% | 0.00%−39.31% | 37.74 | 97.4% | P < 0.0001 | ||
| Giardia intestinalis | 5 (5) | 6.15% | 3.54%−9.41% | 11.03 | 63.8% | P = 0.02 | 0.93 | P = 0.87 |
| Entamoeba histolytica | 2 (2) | 14.20% | 0.00%−38.93% | 5.69 | 82.4% | P = 0.017 | ||
| Entamoeba coli | 3 (3) | 4.8% | 1.66%−9.68% | 6.59 | 69.7% | P = 0.037 | ||
| Cyclospora | 2 (2) | 2.47% | 0.00%−5.47% | 1.19 | 16.2% | P = 0.2747 | ||
| Year | ||||||||
| < 2010 | 6 (6) | 34.95% | 14.28–59.16% | 268.86 | 98.1% | P < 0.0001 | 3.61 | P = 0.666 |
| 2011–2020 | 24 (34) | 20.12% | 13.34–27.89% | 1,15 | 97.1% | P < 0.0001 | 6.54 | P < 0.0001 |
| 2020–2024 | 16 (28) | 16.11% | 10.53–22.60% | 478.48 | 94.4% | P < 0.0001 | 6.57 | P < 0.0001 |
| Diagnostic method | ||||||||
| ELISA | 4 (4) | 20.49% | 11.21–31.70% | 12.54 | 76.1% | P = 0.0057 | 4.07 | P = 0.0767 |
| Parasitological (Microscopy) | 36 (40) | 15.04% | 9.30–21.88% | 1,73 | 97.8% | P < 0.0001 | 7.83 | P < 0.0001 |
| Molecular (PCR) | 24 (25) | 28.34% | 20.43–36.99% | 370.73 | 93.8% | P < 0.0001 | 5.29 | P = 0.001 |
| Country | ||||||||
| China | 11 (13) | 23.79% | 12.53–37.32% | 490.01 | 97.8% | P < 0.0001 | 4.13 | P = 0.445 |
| Colombia | 1 (3) | 11.15% | 0.96–30.27% | 29.48 | 93.2% | P < 0.0001 | ||
| Egypt | 4 (11) | 14.93% | 5.6–27.71% | 269.07 | 96.3% | P < 0.0001 | 8.64 | P < 0.0001 |
| Iran | 6 (7) | 21.93% | 9.47–37.77% | 65.32 | 90.8% | P < 0.0001 | 4.27 | P = 0.0413 |
| Iraq | 3 (3) | 19.29% | 6.87–36.08% | 11.37 | 82.4% | P = 0.0034 | ||
| Malaysia | 3 (3) | 27.92% | 18.28–38.73% | 5.78 | 65.4% | P = 0.0555 | ||
| Poland | 4 (4) | 18.63% | 9.11–30.57% | 21.30 | 85.9% | P < 0.0001 | 8.25 | P = 0.0175 |
| Saudi Arabia | 3 (3) | 39.45% | 20.99–59.63% | 12.79 | 84.4% | P = 0.0017 | ||
| Turkey | 3 (6) | 5.8% | 2.7–10.18% | 18.54 | 73% | P = 0.0023 | 4.21 | P = 0.004 |
| Uzbekistan | 1 (9) | 12.61% | 2.54–28.76% | 619.25 | 98.7% | P < 0.0001 | 15.91 | P = 0.0282 |
The analysis of the distribution of studies indicated a significant concentration in particular countries. Specifically, there are 11 studies originating from China, which collectively encompass 12 datasets. In Saudi Arabia, Malaysia, China, Iran, and Iraq, the pooled prevalence of IPIs was notably higher than in other countries. The highest pooled prevalence rates were observed at 39.45% (95% CI: 20.99%—59.63%) in Saudi Arabia, 27.92% (95% CI: 18.28%—38.73%) in Malaysia, 22.49% (95% CI: 11.90%—35.27%) in China, 23.79% (95% CI: 12.53%—37.72%) in Iran, and 19.29% (95% CI: 6.87%—36.08%) in Iraq.
Results of assessing the association between IPIs and CRC
Compared to the healthy control group, individuals with parasitic infections exhibited a significantly higher likelihood of developing CRC, with an odds ratio of 3.61 (95% CI: 2.41—5.43). As illustrated in Fig. 3, there was also a notable elevation in the prevalence of IPIs among CRC patients. The assessment of statistical heterogeneity indicated substantial variability across the studies, with a Q = 248.39 and I2 = 83.5% (P < 0.001). Furthermore, a significant publication bias was detected, as evidenced by the Egger bias statistic of 0.744 (P = 0.341) (Fig. 4).
Fig. 3.
Forest plot for assessment of odds-ratio of influence of CRC and IPI, according to selected articles used in the meta-analysis using random effects analysis with pooled odds ratio of 3.61 (95% CI: 2.41—5.43)
Fig. 4.
Funnel plot showing the absence of publication bias among the included studies (P = 0.341)
The pooled ORs for protozoan and helminthic infections were found to be 4.24 (95% CI: 2.65 to 6.79) and 1.96 (95% CI: 1.37 to 2.83), respectively. Additionally, the pooled ORs for specific infections, including Cryptosporidium spp., Blastocystis spp., and Giardia intestinalis, were reported as 12.48 (95% CI: 5.82 to 26.79), 3.24 (95% CI: 21.64 to 6.39), and 0.77 (95% CI: 0.44 to 1.36), respectively (Table 3).
Table 3.
The pooled OR of parasitic infection in CRC patients in different subgroups
| Subgroups | Datasets | Heterogeneity | Pooled odd ratio | |||||
|---|---|---|---|---|---|---|---|---|
| Q | I2 | P-value | OR | CI 95% | P-value | |||
| Type of Infection | Protozoan | 57 | 230.92 | 84.8% | P < 0.0001 | 4.24 | 2.65 to 6.79 | P < 0.0001 |
| Helminthic | 11 | 9.03 | 44.6% | P = 0.1077 | 1.96 | 1.37 to 2.83 | P = 0.0001 | |
| Type of Protozoan | Cryptosporidium.spp. | 15 | 24.39 | 63.1% | P < 0.0001 | 12.48 | 5.82 to 26.79 | P < 0.0001 |
| Blastocystis spp. | 19 | 66.59 | 86.5% | P < 0.0001 | 3.24 | 1.64 to 6.39 | P = 0.0007 | |
| Giardia intestinalis | 3 | 4.18 | 52.2% | P = 0.12 | 0.77 | 0.44 to 1.36 | P = 0.35 | |
Results of reviewed case report studies
As shown in Fig. 1, this review identified 15 case reports published between 2001 and 2023. Among these cases, seven patients (46.66%) were male, and eight patients (53.33%) were female. The cases were reported from various countries, including the USA (three studies), Korea (two studies), Colombia, Laos, the Philippines, Tanzania, the Netherlands, Sudan, Japan, China, and Saudi Arabia. The mean age of the patients was 55.62 years. In the studies mentioned, IPIs were detected using microscopic identification, histopathological methods, and molecular diagnostic techniques such as PCR. Furthermore, cancer diagnoses were made through colonoscopy and imaging methods such as computed tomography scans (CT scans). Most of the studies reported helminth contamination, while only two studies documented protozoan contamination. Further details of case report studies included in this review can be found in Table 4.
Table 4.
Base line table of included case report studies
| Author (Ref) | Year | Country | parasite | Age | Gender | parasitological diagnosis methods | cancer diagnosis methods | other signs and symptoms |
|---|---|---|---|---|---|---|---|---|
| Castro et al. [57] | 2023 | Clombia | Blastocystis spp. | 69 | Male | Microscopy, culture, PCR | Colonoscopy | Fever, previous history of intestinal polyps, iron- deficiency anemia |
| Burky et al. [58] | 2022 | Laos | Schistosoma mekongi | 40 | Female | Microscopic and Histopathology | Colonoscopy | Rectal bleeding and proctoscopy, Calcification along the portal venous system |
| Almoghrabi et al. [59] | 2021 | USA | Schistosoma japonicum | 67 | Female | Microscopic | Colonoscopy, Biopsy and CT | Chronic lower abdominal discomfort associated with constipation alternating with diarrhea, decreased appetite and weight loss |
| Sava et al. [60] | 2020 | USA | Strongyloides stercoralis | 70 | Female | Microscopic | CT | Abdominal pain and nonblood diarrhea with associated weight loss |
| Medina et al. [61] | 2019 | Philippines | Schistosoma | 44 | Female | Histopathology | Colonoscopy and histopathology | Constipation and decrease in caliber of stool and weight |
| Kiyani et al. [62] | 2018 | USA | Schistosoma japonicum | 54 | Female | Histopathology | Colonoscopy | During the colonoscopy, 2 small 4-mm flat polyps were removed from the rectum |
| Herman et al. [63] | 2017 | Tanzania | Schistosoma manson | 52 | Male | Microscopic and Histopathology | Sonography and colonoscopy | Abdominal pain, distension, and constipation |
| Furnee et al. [64] | 2015 | Netherlands | Enterobius vermicularis | 68 | Male | Microscopic and Histopathology | Colonoscopy, CT and MRI | Rectal bleeding and change in bowel habits |
| Catalano et al. [65] | 2015 | USA | Strongyloides stercoralis | 47 | Male | Microscopic | Colonoscopy and CT | Fatigue, weight loss and iron deficiency anemia |
| Won et al. [66] | 2015 | Korea | Strongyloides stercoralis | 72 | Female | Microscopic | CT | Lower back pain and intermittent abdominal discomfort with nausea |
| Salim et al. [67] | 2010 | Sudan | Schistosoma mansoni | 35 | Male | Biopsy | CT, Endoscopic and biopsy | Abdominal pain, constipation, and occasional bleeding per rectum |
| Yoo et al. [68] | 2008 | Korea | Anisakis | 50 | Female | Microscopic | Colonoscopy, CT | Abdominal pain, a segmental fold thickening in the ascending colon, a concentric narrowing in the sigmoid colon |
| Mineta et al. [69] | 2006 | Japan | Anisakis | 69 | Male | Microscopic and histopathology | CT, colonoscopy | Abdominal pain, diarrhea, and urticaria, obstruction of the ascending colon and a palpable tumor of the right lower abdomen |
| Li et al. [70] | 2005 | China | Schistosoma japonicum | 57 | Female | Microscopic and histopathology | Colonoscopy | 10-month history of left lower quadrant abdominal pain and a 2-month history of bloody stools, an exophytic fragile neoplasm with an ulcerating surface in the sigmoid colon |
| Al-Mashat [71] | 2001 | Saudi Arabia | Schistosoma | 46 | Male | Microscopic | Biopsy, CT, Colonoscopy | Calcification of the entire wall of the urinary bladder, the entire rectum and part of the sigmoid colon were narrowed, irregular and ulcerated |
Results of reviewed experimental studies
This review included nine experimental studies (Supplementary files 1 and 2). The experimental studies were reported from various countries, including Malaysia (four studies), Mexico (three studies), Germany, and Egypt. There were three in vitro studies related to Blastocystis spp. and human colorectal cancer cells, and HCT116 was implemented. These studies used real-time reverse transcription PCR and MTT assay to determine the interaction between this parasite and the HCT116 cell line. Based on the results of these studies, Blastocystis subtypes increased the proliferation of HCT116, and its antigens are able to downregulate IFN-γ and TNF-α gene expression and upregulate the expression of the IL-6 and NF-κB genes in the HCT116 cell line [72–74]. Moreover, in this review there were 6 in vivo studies on different parasites including Taenia crassiceps [75–77], S. mansoni [78], Heligmosomoides polygyrus [79], and Blastocystis spp. [80], which are summarized in Supplementary file 2. In these studies, BALB/C mice and Wistar rats were implemented. The mentioned studies were conducted on chemically induced colon carcinogenesis and/or colitis-associated colorectal cancer. Their findings indicated that excreted/secreted products derived from T. crassiceps may enhance the effectiveness of 5-fluorouracil on established colon tumors. Additionally, treating mice with these excreted/secreted products resulted in a reduction of inflammatory cytokines such as IL-1β, TNF-α, IL-33, and IL-17, significantly decreasing colon tumorigenesis.
Discussion
IPIs represent a significant global health challenge, affecting an estimated hundreds of millions of individuals worldwide, particularly in tropical and subtropical areas [81]. The pathophysiological outcome of parasitic infections can result in a spectrum of clinical manifestations ranging from mild morbidity to severe, life-threatening conditions [82]. Moreover, IPIs have been increasingly recognized as a significant risk factor for the development of various types of cancer [83]. Chronic infections with parasites, such as Schistosoma spp. and Plasmodium spp., can lead to chronic inflammation, tissue damage, and genetic alterations in the host, thereby creating a microenvironment conducive to cancer development [84]. The pathways by which parasites promote carcinogenesis are complex and involve mechanisms such as the induction of chronic inflammation, DNA damage, and epigenetic alterations [85, 86]. Moreover, some parasites, such as Toxoplasma gondii, have been shown to manipulate the host's immune system, suppressing anti-tumor responses and promoting tumor growth [86]. Furthermore, research has revealed similarities between parasites and cancer cells in their survival strategies within a host, including immune evasion [87]. Therefore, understanding the complex relationship between parasitic infections and cancer is crucial for the development of effective prevention and treatment strategies. In this context, the present study aimed to conduct a systematic review and meta-analysis to estimate the pooled prevalence of IPIs in CRC patients and ORs for association between IPIs and an increased risk of CRC.
Our analysis included 46 case–control and cross-sectional studies in three distinct timeframes. The limited number of articles from the earlier period (1980 to 2008) reflects the emerging stage of research regarding the relationship between IPIs and CRC. The significant increase in publications between 2012 and 2020 indicates a growing interest in the association between parasitology and oncology. This trend may correlate with advancements in diagnostic techniques, which have enabled more accurate detection of parasites [88]. The most recent cohort of studies (2020 to 2024) indicates a growing interest among researchers in exploring the associations of IPIs in CRC [12, 22, 76].
The data, derived from studies conducted across different countries, highlight significant geographical trends and potential correlations between IPIs and the incidence of CRC. A systematic review of global data indicates widespread reports of Blastocystis spp. and Cryptosporidium spp. infections in CRC patients, with a notable prevalence in developing countries including Iran, China, Saudi Arabia, Turkey, Uzbekistan, and Malaysia. The concentration of studies from countries like China, where Schistosoma species are prevalent, reinforces the established link between chronic IPIs and CRC. This association is often attributed to mechanisms such as chronic inflammation, tissue damage, and the promotion of a microenvironment conducive to cancer development [31–42].
Among the included studies, microscopic examination emerged as the predominant diagnostic technique, employed in 36studies (40 datasets). This traditional method has long been recognized as a fast, reliable, and gold standard test for the identification of gastrointestinal parasitic infections. However, it has limitations such as lower sensitivity and specificity compared to molecular method [89, 90]. The notable investigation of PCR methods in 24 studies (25 datasets) signifies a shift towards more advanced and reliable diagnostic techniques in recent years. PCR-based approaches offer critical advantages, such as the detection of low quantities of parasite DNA and the ability to differentiate between species. The uncommon use of ELISA as a primary diagnostic tool in only a small fraction of studies (4 datasets) raises questions about its applicability in this context. While ELISA is effective for detecting parasite-specific antibodies, its suitability for identifying acute infections or directly detecting parasites, a crucial aspect in CRC research, may be limited. Future studies could investigate the utility of combining ELISA with other diagnostic methods to achieve a more comprehensive evaluation of IPIs in CRC patients [91, 92].
In subgroup analysis, the pooled prevalence of protozoan infection among CRC patients was 19.4% (95% CI: 14.39%−24.96%). Analysis revealed that Blastocystis spp. and Cryptosporidium spp. were the most prevalent protozoan parasites in CRC patients. In Taghipour et al. (2022) study, the finding showed a positive association between Cryptosporidium spp. and Blastocystis spp. infections and CRC [93]. In a similar study, Kalantari et al. (2020) found that there was an association between Cryptosporidium spp. infection and CRC [94]. In another study, Toychiev et al. (2018) reported a high prevalence (80%) of Blastocystis spp. among protozoan parasites in CRC patients [37]. Several experimental studies suggest that Blastocystis spp. may enhance the proliferative, invasive, and metastatic capabilities of CRC cells [95]. Specifically, Rajamanikam et al. (2023) found that the ST3 subtype of B. hominis significantly increased the proliferation of the human colorectal carcinoma cell line (HCT116) [96]. In the same direction, research has shown that Cryptosporidium parvum is a potential trigger for intestinal dysplasia [97]. A recent experimental study suggesting that Cryptosporidium parvum infection can alter the host cell's cytoskeleton and disrupt various cellular processes, which may contribute to the abnormal transformation of infected epithelial cells [35]. It appears that immunological and genetic alterations induced by parasites can disrupt host hemostasis, potentially promoting the development of cancerous cells. Furthermore, dysregulation of immune responses within the gut epithelium may contribute to chronic diseases, leading to detrimental consequences for the host, such as tissue damage, inflammation, and an elevated risk of carcinogenesis [98].
Conversely, the pooled prevalence of helminthic infection among CRC patients was 20.79% (95% CI: 8.35%—36.96%). Helminthic infections have a complex and potentially dual role in CRC [99]. While some helminth infections are being explored as potential therapeutics for inflammatory disorders, other helminth infections have been linked to cancer development. Cancers associated with helminth infections include cholangiocarcinoma, hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer [100]. Helminthic infections and tumor progression share biochemical mechanisms and immune response pathways [101]. Chronic helminthic infections modulate the host's immune responses [102]. Like tumors, helminths can subvert the immune response by modulating the environment from pro-inflammatory to anti-inflammatory. Helminths may also promote DNA mutations while also expressing similar structures to tumor cells [37, 103]. Certain helminths, such as Fasciola gigantica and Taenia solium, have been implicated as potential inducers of DNA mutations [104]. Furthermore, many helminthic parasites express mucin O-glycans, including N-acetylgalactosamine O-serine/threonine (Tn), Thomsen-Friedenreich (TF), TK, and sialyl-Tn (sTn) antigens, which are structurally analogous to those found on tumor cells [101].
For example, Echinococcus granulosus expresses Tn, sTn, and TF antigens, and the Tk antigen found on colorectal cancer cells is also present in parasites like Taenia crassiceps, Mesocestoides vogae, and Taenia hydatigena. These similarities could open new paths for cancer research and treatment [105, 106].
The tumor development process that is stimulated by the helminths is complex. Like the tumor microenvironment, helminth infections can alter the immune landscape by increasing immunosuppressive cells and factors (e.g., Tregs, IL-10) [107], decreasing cytotoxic lymphocytes, increasing vascular growth factors, and producing tumor-promoting hormones [108], leading to a pro-tumorigenic state and promoting neoplastic transformation. Schistosoma japonicum, found in a significant percentage of CRC patients, is linked to CRC through mechanisms similar to colitis-induced cancer. Schistosoma induces chronic inflammation, tissue damage, immune evasion, gut dysbiosis, and potentially direct carcinogenic effects, creating a tumor-friendly environment [30, 46, 77, 104]. The pathogenesis of S. japonicum-associated CRC is the result of chronic inflammation produced by egg deposition into the submucosa and mucosa of the colorectum, inducing granuloma formation, cellular infiltration, and ulceration [109]. Chronic inflammation leads to fibrosis, mucosal hyperplasia, and crypt elongation, forming a tumorigenic microenvironment, while reactive oxygen species (ROS) and pro-inflammatory cytokines (e.g., TNF-α, IL-6) from macrophages induce DNA damage and aberrantly regulate tumor suppressor pathways like p53 [110]. Concurrently, S. japonicum-induced immunosuppression allows for coinfection with bacterial pathogens such as Salmonella, which cooperate with the parasitic toxin to degrade mucosal barriers and trigger oncogenic signaling such as Wnt/β-catenin [109, 110]. Molecular alterations involve p53 mutations, epigenetic silencing of tumor suppressors by DNA hypermethylation, and immune evasion by polarization of M2 macrophages [105]. Schistosomal toxins enhance oxidative stress, lipid peroxidation, and DNA adduct formation and disrupt proliferative pathways (TGF-β, MAPK) and apoptosis [111]. This multifactorial interaction of inflammation, bacterial synergy, and molecular disruption is the foundation of the carcinogenic process.
According to an odds ratio analysis, Cryptosporidium spp. and Blastocystis spp. show a particularly strong association (OR = 12.48 and 3.24, respectively), while Giardia intestinalis also presents a notable risk (OR = 0.77). It should be noted that the high statistical heterogeneity observed (I2 = 83.5%, P < 0.001) implies variability in study designs and populations, which may influence the generalizability of these findings. Additionally, the presence of publication bias, as indicated by the Egger statistic (0.744, P = 0.341), raises concerns about the completeness of the evidence base.
Despite the insights gained from this systematic review, it is important to acknowledge several limitations, including i) limited sample sizes in some articles, ii) differences in study designs, iii) diverse methods for identifying IPIs, and iv) insufficient evaluation of variables such as gender, age, and the immunosuppression status of patients. Additionally, the lack of comprehensive data from certain regions may restrict the generalizability of our findings.
Conclusion
In conclusion, this review study revealed that the prevalence of IPIs is relatively high in people with CRC. Moreover, the findings suggest a significant association between IPIs and CRC in comparison to healthy group. Both helminthic and protozoan infections are common among CRC patients, potentially influencing the development and progression of CRC. The interaction between weakened immune function in cancer patients and the immune-regulating effects of parasites may foster a tumor-supportive environment, encouraging cancer development. Further investigations are necessary to clarify the relationship between IPIs and CRC. These results indicate that identifying and treating individuals with IPIs could be an important part of strategies for preventing and managing CRC.
Supplementary Information
Acknowledgements
We would like to thankful to all authors that their valuable publications were included in this study. This study was supported by Toxoplasmosis Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran, (Code number: 20397).
Clinical trial number
Not applicable.
Informed consent
Not applicable.
AI use statement
During the preparation of this work, the authors used AI tools just for enhancing readability, grammar checking and correcting spelling errors. After using this tool, the authors reviewed and edited the content as needed and took responsibility for the publication’s content.
Abbreviations
- CRC
Colorectal cancer
- IPI
Intestinal Parasite Infection
- PRISMA
Preferred Reporting Items for Systematic reviews and Meta-Analyses
Authors’ contributions
M.H., B.B., and M.B. contributed to the data base search. M.H., B.B., M.B., and M.G. performed data extraction. H.Z., S.G., and B.R. were involved in the conceptualization and provided design advice. Statistical analysis was conducted by S. A. H. The original draft was written by M.H., and R.S. All authors have read and approved the final version of the manuscript.
Funding
Not applicable in this study.
Data availability
Raw data and their related analysis are available upon reasonable request from the readers of this article to the corresponding authors of this article by email to Reza.sab.68@gmail.com and Hosseini4030@gmail.com.
Declarations
Ethics approval and consent to participate
The Research Ethics Committees of Mazandaran University of Medical Sciences approved this study (IR.MAZUMS.REC.1403.067).
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Maryam Hataminejad and Bahareh Basirpour co first authorship.
Contributor Information
Seyed Abdollah Hosseini, Email: Hosseini4030@gmail.com.
Reza Saberi, Email: reza.sab.68@gmail.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Raw data and their related analysis are available upon reasonable request from the readers of this article to the corresponding authors of this article by email to Reza.sab.68@gmail.com and Hosseini4030@gmail.com.




