Effect of exposure to RF on cancer risk: A systematic review of human observational studies – Part I:

Abstract

Effect of exposure to RF on cancer risk: A systematic review of human observational studies – Part I: Most researched outcomes (WHO SR 1A) My note: See Biased WHO-commissioned review claims no cancer link Karipidis K, Baaken D, Loney T, Blettner M, Brzozek C, Elwood M, Narh C, Orsini N, Röösli M, Paulo MS, Lagorio S. The effect of exposure to radiofrequency fields on cancer risk in the general and working population: A systematic review of human observational studies – Part I: Most researched outcomes. Environment International (2024), doi: 10.1016/j.envint.2024.108983. Open access paper: doi.org Abstract Background The objective of this review was to assess the quality and strength of the evidence provided by human observational studies for a causal association between exposure to radiofrequency electromagnetic fields (RF-EMF) and risk of the most investigated neoplastic diseases. Methods Eligibility criteria: We included cohort and case-control studies of neoplasia risks in relation to three types of exposure to RF-EMF: near-field, head-localized, exposure from wireless phone use (SR-A); far-field, whole body, environmental exposure from fixed-site transmitters (SR-B); near/far-field occupational exposures from use of hand-held transceivers or RF-emitting equipment in the workplace (SR-C). While no restrictions on tumour type were applied, in the current paper we focus on incidence- based studies of selected “critical” neoplasms of the central nervous system (brain, meninges, pituitary gland, acoustic nerve) and salivary gland tumours (SR-A); brain tumours and leukaemias (SR-B, SR-C). We focussed on investigations of specific neoplasms in relation to specific exposure sources (i.e. E-O pairs), noting that a single article may address multiple E-O pairs. Information sources: Eligible studies were identified by literature searches through Medline, Embase, and EMF-Portal. Risk-of-bias (RoB) assessment: We used a tailored version of the Office of Health Assessment and Translation (OHAT) RoB tool to evaluate each study’s internal validity. At the summary RoB step, studies were classified into three tiers according to their overall potential for bias (low, moderate and high). Data synthesis: We synthesized the study results using random effects restricted maximum likelihood (REML) models (overall and subgroup meta-analyses of dichotomous and categorical exposure variables), and weighted mixed effects models (dose–response meta-analyses of lifetime exposure intensity). Evidence assessment: Confidence in evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results We included 63 aetiological articles, published between 1994 and 2022, with participants from 22 countries, reporting on 119 different E-O pairs. RF-EMF exposure from mobile phones (ever or regular use vs no or non-regular use) was not associated with an increased risk of glioma [meta-estimate of the relative risk (mRR) = 1.01, 95 % CI = 0.89–1.13), meningioma (mRR = 0.92, 95 % CI = 0.82–1.02), acoustic neuroma (mRR = 1.03, 95 % CI = 0.85–1.24), pituitary tumours (mRR = 0.81, 95 % CI = 0.61– 1.06), salivary gland tumours (mRR = 0.91, 95 % CI = 0.78–1.06), or paediatric (children, adolescents and young adults) brain tumours (mRR = 1.06, 95 % CI = 0.74–1.51), with variable degree of across-study heterogeneity (I2 = 0 %-62 %). There was no observable increase in mRRs for the most investigated neoplasms (glioma, meningioma, and acoustic neuroma) with increasing time since start (TSS) use of mobile phones, cumulative call time (CCT), or cumulative number of calls (CNC). Cordless phone use was not significantly associated with risks of glioma [mRR = 1.04, 95 % CI = 0.74–1.46; I2 = 74 %) meningioma, (mRR = 0.91, 95 % CI = 0.70–1.18; I2 = 59 %), or acoustic neuroma (mRR = 1.16; 95 % CI = 0.83–1.61; I2 = 63 %). Exposure from fixed-site transmitters (broadcasting antennas or base stations) was not associated with childhood leukaemia or paediatric brain tumour risks, independently of the level of the modelled RF exposure. Glioma risk was not significantly increased following occupational RF exposure (ever vs never), and no differences were detected between increasing categories of modelled cumulative exposure levels. Discussion In the sensitivity analyses of glioma, meningioma, and acoustic neuroma risks in relation to mobile phone use (ever use, TSS, CCT, and CNC) the presented results were robust and not affected by changes in study aggregation. In a leave-one-out meta-analyses of glioma risk in relation to mobile phone use we identified one influential study. In subsequent meta-analyses performed after excluding this study, we observed a substantial reduction in the mRR and the heterogeneity between studies, for both the contrast Ever vs Never (regular) use (mRR = 0.96, 95 % CI = 0.87–1.07, I2 = 47 %), and in the analysis by increasing categories of TSS (“<5 years”: mRR = 0.97, 95 % CI = 0.83–1.14, I2 = 41 %; “5-9 years ”: mRR = 0.96, 95 % CI = 0.83–1.11, I2 = 34 %; “10+ years”: mRR = 0.97, 95 % CI = 0.87–1.08, I2 = 10 %). There was limited variation across studies in RoB for the priority domains (selection/attrition, exposure and outcome information), with the number of studies evenly classified as at low and moderate risk of bias (49 % tier-1 and 51 % tier-2), and no studies classified as at high risk of bias (tier-3). The impact of the biases on the study results (amount and direction) proved difficult to predict, and the RoB tool was inherently unable to account for the effect of competing biases. However, the sensitivity meta-analyses stratified on bias-tier, showed that the heterogeneity observed in our main meta-analyses across studies of glioma and acoustic neuroma in the upper TSS stratum (I2 = 77 % and 76 %), was explained by the summary RoB-tier. In the tier-1 study subgroup, the mRRs (95 % CI; I2) in long-term (10+ years) users were 0.95 (0.85–1.05; 5.5 %) for glioma, and 1.00 (0.78–1.29; 35 %) for acoustic neuroma. The time-trend simulation studies, evaluated as complementary evidence in line with a triangulation approach for external validity, were consistent in showing that the increased risks observed in some case-control studies were incompatible with the actual incidence rates of glioma/brain cancer observed in several countries and over long periods. Three of these simulation studies consistently reported that RR estimates > 1.5 with a 10+ years induction period were definitely implausible, and could be used to set a “credibility benchmark”. In the sensitivity meta-analyses of glioma risk in the upper category of TSS excluding five studies reporting implausible effect sizes, we observed strong reductions in both the mRR [mRR of 0.95 (95 % CI = 0.86–1.05)], and the degree of heterogeneity across studies (I2 = 3.6 %). Conclusions Consistently with the published protocol, our final conclusions were formulated separately for each exposure-outcome combination, and primarily based on the line of evidence with the highest confidence, taking into account the ranking of RF sources by exposure level as inferred from dosimetric studies, and the external coherence with findings from time-trend simulation studies (limited to glioma in relation to mobile phone use). For near field RF-EMF exposure to the head from mobile phone use, there was moderate certainty evidence that it likely does not increase the risk of glioma, meningioma, acoustic neuroma, pituitary tumours, and salivary gland tumours in adults, or of paediatric brain tumours. For near field RF-EMF exposure to the head from cordless phone use, there was low certainty evidence that it may not increase the risk of glioma, meningioma or acoustic neuroma. For whole-body far-field RF-EMF exposure from fixed-site transmitters (broadcasting antennas or base stations), there was moderate certainty evidence that it likely does not increase childhood leukaemia risk and low certainty evidence that it may not increase the risk of paediatric brain tumours. There were no studies eligible for inclusion investigating RF-EMF exposure from fixed-site transmitters and critical tumours in adults. For occupational RF-EMF exposure, there was low certainty evidence that it may not increase the risk of brain cancer/glioma, but there were no included studies of leukemias (the second critical outcome in SR- C). The evidence rating regarding paediatric brain tumours in relation to environmental RF exposure from fixed-site transmitters should be interpreted with caution, due to the small number of studies. Similar interpretative cautions apply to the evidence rating of the relation between glioma/brain cancer and occupational RF exposure, due to differences in exposure sources and metrics across the few included studies. Other This project was commissioned and partially funded by the World Health Organization (WHO). Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; and ARPANSA as a WHO Collaborating Centre for Radiation Protection. Registration: PROSPERO CRD42021236798. Published protocol: [(Lagorio et al., 2021) DOI doi.org]. Open access paper: sciencedirect.com

AI evidence extraction

Main findings

This systematic review/meta-analysis of 63 human observational articles (1994–2022) reported no association between mobile phone use and risks of glioma, meningioma, acoustic neuroma, pituitary tumours, salivary gland tumours, or paediatric brain tumours, and found no dose–response increase with time since start, cumulative call time, or number of calls. It also reported no association between fixed-site transmitter exposure and childhood leukaemia or paediatric brain tumours, and no significant increase in glioma/brain cancer with occupational RF exposure in the included studies. The authors concluded moderate-certainty evidence that mobile phone RF exposure likely does not increase risk for several adult CNS/salivary tumours and paediatric brain tumours, with lower-certainty evidence for cordless phones, fixed-site transmitters (paediatric brain tumours), and occupational exposure.

Outcomes measured

• Glioma
• Meningioma
• Acoustic neuroma
• Pituitary tumours
• Salivary gland tumours
• Paediatric brain tumours
• Childhood leukaemia
• Brain cancer (occupational)

Limitations

• Evidence ratings for paediatric brain tumours in relation to environmental RF exposure from fixed-site transmitters should be interpreted with caution due to a small number of studies.
• Interpretation cautions for glioma/brain cancer and occupational RF exposure due to differences in exposure sources and metrics across the few included studies.
• The impact of biases on study results was difficult to predict, and the risk-of-bias tool could not account for competing biases (as described by the authors).
• No eligible studies investigated fixed-site transmitter exposure and critical tumours in adults.
• No included studies of leukemias for occupational RF exposure (second critical outcome in SR-C).

Suggested hubs

• cell-phones (0.95)
  Primary exposure category includes near-field head exposure from mobile phone use with multiple tumour outcomes.
• occupational-exposure (0.7)
  Includes occupational RF exposure from hand-held transceivers/RF-emitting equipment and brain cancer/glioma outcomes.
• who-icnirp (0.65)
  Project was commissioned and partially funded by WHO and uses GRADE/OHAT methods relevant to WHO evidence assessments.

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    "publication_year": null,
    "study_type": "systematic_review",
    "exposure": {
        "band": "RF",
        "source": "mobile phone; cordless phone; fixed-site transmitters (broadcasting antennas/base stations); occupational RF sources (hand-held transceivers/RF-emitting equipment)",
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": "Assessed metrics including time since start of use, cumulative call time, and cumulative number of calls; occupational cumulative exposure categories (modelled)"
    },
    "population": "General and working populations; includes paediatric populations for some outcomes",
    "sample_size": null,
    "outcomes": [
        "Glioma",
        "Meningioma",
        "Acoustic neuroma",
        "Pituitary tumours",
        "Salivary gland tumours",
        "Paediatric brain tumours",
        "Childhood leukaemia",
        "Brain cancer (occupational)"
    ],
    "main_findings": "This systematic review/meta-analysis of 63 human observational articles (1994–2022) reported no association between mobile phone use and risks of glioma, meningioma, acoustic neuroma, pituitary tumours, salivary gland tumours, or paediatric brain tumours, and found no dose–response increase with time since start, cumulative call time, or number of calls. It also reported no association between fixed-site transmitter exposure and childhood leukaemia or paediatric brain tumours, and no significant increase in glioma/brain cancer with occupational RF exposure in the included studies. The authors concluded moderate-certainty evidence that mobile phone RF exposure likely does not increase risk for several adult CNS/salivary tumours and paediatric brain tumours, with lower-certainty evidence for cordless phones, fixed-site transmitters (paediatric brain tumours), and occupational exposure.",
    "effect_direction": "no_effect",
    "limitations": [
        "Evidence ratings for paediatric brain tumours in relation to environmental RF exposure from fixed-site transmitters should be interpreted with caution due to a small number of studies.",
        "Interpretation cautions for glioma/brain cancer and occupational RF exposure due to differences in exposure sources and metrics across the few included studies.",
        "The impact of biases on study results was difficult to predict, and the risk-of-bias tool could not account for competing biases (as described by the authors).",
        "No eligible studies investigated fixed-site transmitter exposure and critical tumours in adults.",
        "No included studies of leukemias for occupational RF exposure (second critical outcome in SR-C)."
    ],
    "evidence_strength": "high",
    "confidence": 0.85999999999999998667732370449812151491641998291015625,
    "peer_reviewed_likely": "unknown",
    "stance": "reassurance",
    "stance_confidence": 0.83999999999999996891375531049561686813831329345703125,
    "summary": "This WHO-commissioned systematic review/meta-analysis assessed human observational evidence on RF-EMF exposure and risk of selected, commonly studied cancers. Across 63 articles and 119 exposure–outcome pairs, mobile phone use was not associated with increased risks of several adult CNS/salivary tumours or paediatric brain tumours, and no dose–response increase was observed with longer or greater phone use. Fixed-site transmitter exposure was not associated with childhood leukaemia or paediatric brain tumours, and occupational RF exposure was not linked to increased glioma/brain cancer in the included studies, though some evidence ratings were cautioned due to few studies and heterogeneous exposure metrics.",
    "key_points": [
        "Included cohort and case-control studies evaluating near-field head exposure (mobile/cordless phones), far-field environmental exposure (base stations/broadcast antennas), and occupational RF exposure.",
        "Mobile phone use (ever/regular vs none/non-regular) was not associated with glioma, meningioma, acoustic neuroma, pituitary tumours, salivary gland tumours, or paediatric brain tumours in the reported meta-analyses.",
        "No observable increase in risk estimates was reported with increasing time since start of mobile phone use, cumulative call time, or cumulative number of calls for the most investigated tumours.",
        "Cordless phone use was not significantly associated with glioma, meningioma, or acoustic neuroma in the reported meta-analyses.",
        "Modelled exposure from fixed-site transmitters was not associated with childhood leukaemia or paediatric brain tumour risk, regardless of exposure level.",
        "Occupational RF exposure (ever vs never and cumulative exposure categories) was not associated with increased glioma/brain cancer risk in the included studies, but conclusions were limited by few studies and varying exposure metrics."
    ],
    "categories": [
        "Cancer",
        "Radiofrequency (RF)",
        "Mobile Phones",
        "Base Stations & Environmental RF",
        "Occupational Exposure",
        "Systematic Reviews & Meta-analyses"
    ],
    "tags": [
        "Systematic Review",
        "Meta-Analysis",
        "Human Observational Studies",
        "Radiofrequency EMF",
        "Mobile Phone Use",
        "Cordless Phones",
        "Base Stations",
        "Broadcast Antennas",
        "Occupational RF Exposure",
        "Glioma",
        "Meningioma",
        "Acoustic Neuroma",
        "Paediatric Brain Tumours",
        "Childhood Leukaemia",
        "GRADE"
    ],
    "keywords": [
        "RF-EMF",
        "radiofrequency",
        "mobile phone",
        "cordless phone",
        "fixed-site transmitters",
        "base stations",
        "broadcasting antennas",
        "occupational exposure",
        "glioma",
        "meningioma",
        "acoustic neuroma",
        "pituitary tumours (adenoma) risk? (as stated: pituitary tumours)"
    ],
    "suggested_hubs": [
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            "slug": "cell-phones",
            "weight": 0.9499999999999999555910790149937383830547332763671875,
            "reason": "Primary exposure category includes near-field head exposure from mobile phone use with multiple tumour outcomes."
        },
        {
            "slug": "occupational-exposure",
            "weight": 0.6999999999999999555910790149937383830547332763671875,
            "reason": "Includes occupational RF exposure from hand-held transceivers/RF-emitting equipment and brain cancer/glioma outcomes."
        },
        {
            "slug": "who-icnirp",
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            "reason": "Project was commissioned and partially funded by WHO and uses GRADE/OHAT methods relevant to WHO evidence assessments."
        }
    ],
    "social": {
        "tweet": "Systematic review/meta-analysis (63 observational studies, 1994–2022) found no association between mobile phone RF exposure and risks of glioma, meningioma, acoustic neuroma, pituitary, salivary gland, or paediatric brain tumours; no dose–response with longer use. Fixed-site transmitters and occupational RF also showed no increased risks in included studies (with cautions where evidence was sparse).",
        "facebook": "A 2024 systematic review/meta-analysis of 63 human observational studies assessed RF-EMF exposure (mobile/cordless phones, base stations/broadcast antennas, and occupational sources) and cancer risk. The review reported no increased risks for several commonly studied tumours with mobile phone use and no dose–response with longer or heavier use. It also found no association for childhood leukaemia or paediatric brain tumours with fixed-site transmitter exposure, and no increased glioma/brain cancer risk with occupational RF exposure in included studies, noting caution where few studies were available.",
        "linkedin": "Environment International (2024) systematic review/meta-analysis of human observational studies (63 articles; 119 exposure–outcome pairs) evaluated RF-EMF exposure from mobile/cordless phones, fixed-site transmitters, and occupational sources. Reported meta-analyses found no association between mobile phone use and risks of glioma, meningioma, acoustic neuroma, pituitary tumours, salivary gland tumours, or paediatric brain tumours, and no dose–response with time since start/cumulative use. Fixed-site transmitter exposure was not associated with childhood leukaemia or paediatric brain tumours, and occupational RF exposure was not linked to increased glioma/brain cancer in included studies, with cautions where evidence was limited."
    }
}

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