背景:本综述的目的是评估人类观察研究提供的证据的质量和强度,以证明暴露于射频电磁场(RF-EMF)与大多数研究的肿瘤疾病的风险之间存在因果关系。
方法:合格标准:我们纳入了与三种类型的RF-EMF暴露有关的肿瘤形成风险的队列和病例对照研究:近场,头部局部化,无线电话使用暴露(SR-A);远场,整个身体,固定站点发射器(SR-B)的环境暴露;在工作场所使用手持式收发器或RF发射设备(SR-C)的近/远场职业暴露。虽然对肿瘤类型没有限制,在当前的论文中,我们专注于对选定的“关键”中枢神经系统肿瘤(脑,脑膜,脑垂体,听神经)和唾液腺肿瘤(SR-A);脑肿瘤和白血病(SR-B,SR-C)。我们专注于与特定暴露源(即E-O对)相关的特定肿瘤的调查,注意,一篇文章可能涉及多个E-O对。
方法:通过Medline的文献检索确定了符合条件的研究,Embase,和EMF门户。偏倚风险(RoB)评估:我们使用了健康评估和翻译办公室(OHAT)RoB工具的定制版本来评估每个研究的内部有效性。在总结RoB步骤中,根据研究的总体偏见潜力将研究分为三个层次(低,中等和高)。
结果:我们使用随机效应限制最大似然(REML)模型(二分和分类暴露变量的总体和亚组荟萃分析)综合了研究结果,和加权混合效应模型(终生暴露强度的剂量-反应荟萃分析)。证据评估:使用建议分级评估对证据的信心,评估,开发和评估(等级)方法。
结果:我们纳入了63篇病因学文章,1994年至2022年出版,来自22个国家的参与者,报告119个不同的E-O对。手机的RF-EMF暴露(曾经或定期使用与没有或不定期使用)与胶质瘤的风险增加无关[相对风险(mRR)的meta估计=1.01,95%CI=0.89-1.13),脑膜瘤(mRR=0.92,95%CI=0.82-1.02),听神经瘤(mRR=1.03,95%CI=0.85-1.24),垂体肿瘤(mRR=0.81,95%CI=0.61-1.06),唾液腺肿瘤(mRR=0.91,95%CI=0.78-1.06),或儿科(儿童,青少年和年轻人)脑肿瘤(mRR=1.06,95%CI=0.74-1.51),具有不同程度的跨研究异质性(I2=0%-62%)。对于研究最多的肿瘤(神经胶质瘤,脑膜瘤,和听神经瘤)随着手机开始(TSS)使用时间的增加,累计通话时间(CCT),或累计通话次数(CNC)。无绳电话使用与脑膜瘤[mRR=1.04,95%CI=0.74-1.46;I2=74%](mRR=0.91,95%CI=0.70-1.18;I2=59%),或听神经瘤(mRR=1.16;95%CI=0.83-1.61;I2=63%)。固定站点发射器(广播天线或基站)的暴露与儿童白血病或小儿脑瘤风险无关,与模拟的射频暴露水平无关。职业性射频暴露后胶质瘤风险没有显著增加(从未与从未),并且在建模的累积暴露水平的增加类别之间没有检测到差异。
结论:在胶质瘤的敏感性分析中,脑膜瘤,和与手机使用相关的听神经瘤风险(曾经使用过,TSS,CCT,和CNC)提出的结果是稳健的,不受研究聚集变化的影响。在与手机使用相关的神经胶质瘤风险的留一荟萃分析中,我们确定了一项有影响力的研究。在排除本研究后进行的后续荟萃分析中,我们观察到mRR的大幅降低和研究之间的异质性,对于对比剂,从未使用(常规)(mRR=0.96,95%CI=0.87-1.07,I2=47%),在增加TSS类别的分析中(“<5年”:mRR=0.97,95%CI=0.83-1.14,I2=41%;“5-9年”:mRR=0.96,95%CI=0.83-1.11,I2=34%;“10年”:mRR=0.97,95%CI=0.87-1.08,I2=10%)。RoB中优先领域的研究差异有限(选择/减员,暴露和结果信息),研究数量均匀地分为低和中等偏倚风险(49%的一级和51%的二级),没有被归类为高偏倚风险的研究(第3层)。偏差对研究结果(数量和方向)的影响难以预测,而RoB工具本来就无法解释竞争偏见的影响。然而,敏感性荟萃分析按偏倚层分层,表明,在我们的主要荟萃分析中观察到的异质性,在TSS上层的神经胶质瘤和听神经瘤的研究中(I2=77%和76%),由摘要RoB-tier解释。在一级研究亚组中,长期(10年以上)用户的mRRs(95%CI;I2)是胶质瘤的0.95(0.85-1.05;5.5%),听神经瘤为1.00(0.78-1.29;35%)。时间趋势模拟研究,根据外部有效性的三角剖分方法评估为补充证据,这表明在一些病例对照研究中观察到的增加的风险与在几个国家和长期观察到的神经胶质瘤/脑癌的实际发病率不相容。这些模拟研究中的三个一致报道,在10年以上的诱导期,RR估计值>1.5肯定是不可信的,并可用于设置“信誉基准”。在TSS上层类胶质瘤风险的敏感性荟萃分析中,不包括5项报告不合理效应大小的研究,我们观察到mRR[mRR为0.95(95%CI=0.86-1.05)]的显著降低,以及不同研究的异质性程度(I2=3.6%)。
结论:与已发布的方案一致,我们的最终结论是针对每个暴露-结果组合单独制定的,主要基于最高可信度的证据,考虑到从剂量学研究中推断的按暴露水平对RF源的排名,以及与时间趋势模拟研究结果的外部一致性(仅限于与手机使用有关的神经胶质瘤)。对于从手机使用到头部的近场RF-EMF暴露,有适度的确定性证据表明它可能不会增加神经胶质瘤的风险,脑膜瘤,听神经瘤,垂体肿瘤,成人的唾液腺肿瘤,或小儿脑肿瘤。对于从无绳电话使用到头部的近场RF-EMF暴露,有低确定性的证据表明它可能不会增加神经胶质瘤的风险,脑膜瘤或听神经瘤。对于来自固定站点发射器(广播天线或基站)的全身远场RF-EMF暴露,有中度确定性证据表明它可能不会增加儿童白血病的风险,而低确定性证据表明它可能不会增加儿童脑肿瘤的风险.没有适合纳入研究的研究来自固定站点发射器和成人关键肿瘤的RF-EMF暴露。对于职业性RF-EMF暴露,有低确定性证据表明它可能不会增加脑癌/神经胶质瘤的风险,但没有纳入白血病(SR-C的第二个关键结局)的研究.应谨慎解释儿科脑肿瘤与固定部位发射器环境射频暴露相关的证据评级。由于研究数量少。类似的解释性警告适用于神经胶质瘤/脑癌与职业性射频暴露之间关系的证据评级。由于少数纳入研究的暴露来源和指标存在差异。
■该项目由世界卫生组织(WHO)委托和部分资助。共同供资由新西兰卫生部提供;IstitutoSuperiorediSanità作为世卫组织辐射与健康合作中心;ARPANSA作为世卫组织辐射防护合作中心。
背景:PROSPEROCRD42021236798。公布的协议:[(Lagorio等人,2021)DOIhttps://doi.org/10.1016/j。envint.2021.106828]。
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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
UNASSIGNED: 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.
BACKGROUND: PROSPERO CRD42021236798. Published protocol: [(Lagorio et al., 2021) DOI https://doi.org/10.1016/j.envint.2021.106828].