The effect of exposure to radiofrequency fields on cancer risk in the general and working population: A systematic review of human observational studies - Part II: Less researched outcomes.
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BACKGROUND: In the framework of the World Health Organization assessment of health effects of exposure to radiofrequency electromagnetic fields (RF-EMF), we have conducted a systematic review of human observational studies on the association between exposure to RF-EMF and risk of neoplastic diseases. Due to the extremely large number of included exposure types/settings and neoplasm combinations, we decided to present the review findings in two separate papers. In the first one we addressed the most investigated exposure-outcome pairs (e.g. glioma, meningioma, acoustic neuroma in relation to mobile phone use, or risk childhood leukemia in relation to environmental exposure from fixed-site transmitters) (Karipidis et al., 2024). Here, we report on less researched neoplasms, which include lymphohematopoietic system tumours, thyroid cancer and oral cavity/pharynx cancer, in relation to wireless phone use, or occupational RF exposure. METHODS: Eligibility criteria: We included cohort and case-control studies of neoplasia risks in relation to three types of exposure to RF-EMF: 1. exposure from wireless phone use; 2. environmental exposure from fixed-site transmitters; 3. occupational exposures. In the current paper, we focus on less researched neoplasms including leukaemia, non-Hodgkin's lymphoma and thyroid cancer in mobile phone users; lymphohematopoietic system tumours and oral cavity/pharynx cancer in exposed workers. We focussed on investigations of specific neoplasms in relation to specific exposure sources (termed exposure-outcome pair, abbreviated E-O pairs), noting that a single article may address multiple E-O pairs. INFORMATION SOURCES: Eligible studies were identified by predefined 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. Then, the studies were classified into three tiers according to their overall potential for bias (low, moderate and high) in selected, predefined and relevant bias domains. DATA SYNTHESIS: We synthesized the study results using random effects restricted maximum likelihood (REML) models. Evidence assessment: Confidence in evidence was assessed according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: We included 26 articles, which were published between 1988 and 2019, with participants from 10 countries, reporting on 143 different E-O pairs, including 65 different types of neoplasms. Of these, 19 E-O pairs satisfied the criteria for inclusion in quantitative syntheses of the evidence regarding the risks of leukaemia, non-Hodgkin's lymphoma or thyroid cancer in relation to mobile phone use, and the risks of lymphohematopoietic system tumours or oral cavity/pharynx cancer following occupational exposure to RF-EMF. RF-EMF exposure from mobile phones (ever or regular use vs no or non-regular use) was not associated with an increased risk of leukaemia [meta-estimate of the relative risk (mRR) = 0.99, 95 % CI 0.91-1.07, 4 studies), non-Hodgkin's lymphoma (mRR = 0.99, 95 % CI = 0.92-1.06, 5 studies), or thyroid cancer (mRR = 1.05, 95 % CI = 0.88-1.26, 3 studies). Long-term (10 + years) mobile phone use was also not associated with risk of leukaemia (mRR = 1.03, 95 % CI 0.85-1.24, 3 studies), non-Hodgkin lymphoma (mRR = 0.99, 95 % CI 0.86-1.15, 3 studies), or thyroid cancer (no pooled estimate given the small number of studies). There were not sufficient studies of any specific neoplasms to perform dose-response meta-analyses for either cumulative call time or cumulative number of calls; individual studies did not show statistically significant associations between lifetime intensity of mobile phone use and any specific neoplasm. Occupational RF-EMF exposure (exposed vs unexposed) was not associated with an increased risk of lymphohematopoietic system tumours (mRR = 1.03, 95 % CI = 0.87-1.28, 4 studies) or oral cavity/pharynx cancer (mRR = 0.68, 95 % CI 0.42-1.11, 3 studies). There were not sufficient studies of any specific neoplasms to perform meta-analysis on the intensity or duration of occupational RF-EMF exposure; individual studies did not show statistically significant associations with either of those exposure metrics and any specific neoplasms. The small number of studies, and of exposed cases in some instances, hampered the assessment of the statistical heterogeneity in findings across studies in the meta-analyses. Based on the summary risk of bias, most studies included in the quantitative evidence syntheses were classified at moderate risk of bias. The most critical issue was exposure information bias, especially for occupational studies where the exposure characterization was rated at high risk of bias for all included studies. Outcome information bias was an issue in mortality-based occupational cohort studies investigating non-rapidly fatal neoplasms. Further, the healthy subscriber effect, and (at a lesser extent) the healthy worker effect, were identified as plausible explanations of the decreased risks observed in some studies. The association of RF-EMF exposure from wireless phone use, or workplace equipment/devices, with other important neoplasms was reported by only one or two studies per tumour, so no quantitative evidence syntheses were conducted on these outcomes. It is noted that there were generally no statistically significant exposure-outcome associations for any combinations, independently of the exposure metric and level, with a few studies reporting decreased risks (especially for smoking-related cancers). There was only one study which assessed the effect of RF-EMF exposure from fixed-site transmitters on less researched neoplasms and it reported no statistically significant associations between exposure from base stations and risk of lymphomas overall, lymphoma subtypes, or chronic lymphatic leukaemia in adults. CONCLUSIONS: For near field RF-EMF exposure to the head from mobile phones, there was low certainty of evidence that it does not increase the risk of leukaemia, non-Hodgkin's lymphoma or thyroid cancer. For occupational RF-EMF exposure, there was very low certainty of evidence that it does not increase the risk of lymphohematopoietic system tumours or oral cavity/pharynx cancer. There was not sufficient evidence to assess the effect of whole-body far-field RF-EMF exposure from fixed-site transmitters (broadcasting antennas or base stations), or the effect of RF-EMF from any source on any other important neoplasms. 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 https://doi.org/10.1016/j.envint.2021.106828].