In Vivo Studies on Radiofrequency (100 kHz–300 GHz) Electromagnetic Field Exposure and Cancer: A Systematic Review

2023 · Mixed · High evidence

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MixedHigh evidencePaper 582

Study snapshot

Publicationmanual · 2023

Study typesystematic_review

Reported directionMixed

Evidence ratingHigh

Abstract

In Vivo Studies on Radiofrequency (100 kHz–300 GHz) Electromagnetic Field Exposure and Cancer: A Systematic Review Pinto R, Ardoino L, Villani P, Marino C. In Vivo Studies on Radiofrequency (100 kHz–300 GHz) Electromagnetic Field Exposure and Cancer: A Systematic Review. International Journal of Environmental Research and Public Health. 2023; 20(3):2071. doi: 10.3390/ijerph20032071. Abstract The increasing exposure of the human population to radiofrequency electromagnetic fields has increased concern about its possible health effects. The aim of this systematic review is to provide an update of the state of the research on this topic, through a quantitative analysis, to assess the increased risk of tumor incidence in laboratory animals (rodents) without limitations of species, strain, sex or genotype. The review was conducted according to the PRISMA guideline and individual studies were assessed by referring to the OHAT Risk of Bias Rating Tool for Human and Animal Studies. A total of 27 studies were considered eligible for the evaluation of tumor incidence; a meta-analysis was carried out on 23 studies to assess the possible increased risk of both malignant and benign tumors onset at the systemic level or in different organs/tissues. A significant association between exposure to RF and the increased/decreased risk of cancer does not result from the meta-analysis in most of the considered tissues. A significant increased/decreased risk can be numerically observed only in heart, CNS/brain, and intestine for malignant tumors. Nevertheless, the assessment of the body of evidence attributes low or inadequate evidence for an association between RF exposure and the onset of neoplasm in all tissues. Conclusions This systematic review analyzed the experimental data extracted from 27 eligible articles regarding the onset of neoplasms in laboratory rodents exposed to EMF-RF; a quantitative analysis (meta-analysis) was conducted on 23 papers. Each study was ex amined for possible methodological limits and the RoB was evaluated. A total of 25 organs/tumors were analyzed for malignant tumors and 16 for benign tumors to assess the confidence in the body of evidence of the carcinogenic effects. Starting from a “high quality” grade, a general feature for randomized in vivo studies [5], all items underwent a quality downgrade due to “serious” or “very serious” limitations in the experimental design, mainly caused by a low number of animals in sham groups. A further downgrade was determined by the classification of all studies as “some con cerns” for bias, even without taking into account the conflict of interest. The results obtained after subgrouping analysis by species (rats vs. mice) allowed an upgrade of the certainty of the evidence for many types of malignant and benign tumors. The lack of a dose–response relationship in all the analyzed samples did not allow for further upgrades. Overall, these evaluations have determined a confidence rating from very low (heart sample for malignant tumors and CNS sample for benign ones) to moderate, resulting in 28 of 34 inadequate or insufficient health evidence for a definitive assessment of the association between EMF-RF exposure and carcinogenesis in vivo. This lack of certainty in the conclusions mainly derives from a very cautious GRADE approach, which does not appear entirely justified in this case given that the considered articles present a good homogeneity, both in the methods and in the results, providing adequate answers for the aims of this study. In this regard, it should be considered that, although in recent years the use of systematic reviews has been extended to experimental laboratory studies, the main guidelines [4,5] were developed considering the clinical tri- als. The different approach between clinical and laboratory works has highlighted some methodological difficulties for the application of grade procedures, which could be better analyzed in order to improve the guidelines for the future systematic reviews on animal studies. Furthermore, it should be considered that the inclusion of only English-language papers may have represented a limitation of this systematic review. In conclusion, the inadequate/insufficient health evidence found does not allow this systematic review to give additional information for the integration of present regulatory frameworks. Otherwise, this review updates the state of the art of research on in vivo RF-EMF experiments related to carcinogenesis and, for future research in this field, it emphasizes the need of an appropriate experimental design that takes into account the animal number and the sample number used for the sham control groups. Future work will be the update of this review as required in [4]; in fact, the question of this review is of continuing importance to decision makers and the availability of new data or new methods would have a meaningful impact on the review findings. Moreover, a review update provides an opportunity for the scope, eligibility criteria and methods used in the review to be revised. Open access paper: mdpi.com

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typesystematic_review

Effect directionmixed

PopulationLaboratory rodents (rats and mice)

Sample sizeNot supplied

ExposureRF

Evidence strengthHighConfidence: 78% · Peer reviewed: yes

Main findings

Across 23 in vivo rodent studies included in meta-analysis (27 eligible overall), the authors report that most tissues showed no significant association between RF exposure and increased or decreased cancer risk. Numerically significant increased/decreased risks were observed only for malignant tumors in heart, CNS/brain, and intestine, but the overall body of evidence was rated low or inadequate/insufficient for an association across tissues.

Outcomes measured

Tumor incidence (malignant and benign)
Organ/tissue-specific neoplasm outcomes (e.g., heart, CNS/brain, intestine)

Limitations

Many studies had serious or very serious experimental design limitations, including low numbers of animals in sham control groups.
All studies were classified as having “some concerns” for risk of bias (conflict of interest not considered in this rating).
Lack of dose–response relationship across analyzed samples limited certainty upgrades.
Only English-language papers were included.
Authors note methodological challenges applying GRADE-like approaches developed for clinical trials to animal laboratory studies.

View raw extracted JSON

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  "exposure": {
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  "effect_direction": "mixed",
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    "PRISMA methods were used and individual studies were assessed with the OHAT Risk of Bias tool.",
    "Twenty-seven studies were eligible for tumor-incidence evaluation and 23 were included in meta-analysis.",
    "Most tissues showed no significant association between RF exposure and malignant or benign tumor risk in the meta-analysis.",
    "Numerically significant increased/decreased risks were observed only for malignant tumors in heart, CNS/brain, and intestine.",
    "The body of evidence was rated low to inadequate/insufficient across tissues due to design limitations and risk-of-bias concerns.",
    "The authors highlight small sham control group sizes and lack of dose–response as key issues for certainty.",
    "The review emphasizes improved experimental design and suggests future updates as new data emerge."
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    "Animal Studies",
    "Cancer",
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    "tweet": "Systematic review (2023) of in vivo rodent studies on RF-EMF (100 kHz–300 GHz) and cancer: meta-analysis of 23 studies found no significant associations in most tissues; evidence rated low/inadequate due to design and bias concerns.",
    "facebook": "A 2023 systematic review of rodent experiments on radiofrequency EMF exposure (100 kHz–300 GHz) and tumor incidence analyzed 27 eligible studies (23 in meta-analysis). Most tissues showed no significant associations, and overall evidence was rated low or inadequate/insufficient due to methodological limitations and risk-of-bias concerns.",
    "linkedin": "Pinto et al. (2023) systematically reviewed in vivo rodent studies of RF-EMF exposure (100 kHz–300 GHz) and cancer outcomes (27 eligible; 23 in meta-analysis). Most tissues showed no significant associations; overall certainty was downgraded due to experimental design limitations (e.g., small sham groups), risk-of-bias concerns, and lack of dose–response."
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Identifiers and source

DOI: 10.3390/ijerph20032071
PubMed: Not supplied

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