Background

Exposure to radiofrequency electromagnetic fields (RF-EMF, 100 kHz – 300 GHz) emitted by wireless communication technologies is pervasive and ubiquitous. Concern has been raised about possible adverse effects to human health. In 2011 the International Agency for Research on Cancer has classified RF-EMF as possibly carcinogenic to humans, highlighting that the evidence is weak and far from conclusive. Updated systematic reviews of the scientific literature on this topic are lacking, especially for mechanistic studies.

Objectives

To develop a protocol for a systematic review of experimental studies investigating genotoxic effects induced by RF-EMF in in vitro cellular models. Genotoxicity is one of the key-biological indicators of carcinogenicity, and the most common characteristics of established carcinogens. The predefined procedures for conducting the systematic review are outlined below.

Methods

We will follow the guidelines developed by the National Toxicology Program-Office of Health Assessment and Translation (NTP-OHAT), adapted to the evaluation of in vitro studies.

Eligibility criteria

We will include experimental in vitro studies addressing the relationship between controlled exposures to RF-EMF and genotoxicity in mammalian cells only. Eligibility for inclusion will be further restricted to peer reviewed articles reporting findings from primary studies.

Information sources

We will search the scientific literature databases NCBI PubMed, Web of Science, and EMF-Portal. No filter on publication date will be applied. Only studies published in English will be considered. The reference lists of the included papers and available reviews will be screened for unidentified relevant papers. References will be managed through Endnote X9 software.

Data extraction and synthesis of results

Data from included papers will be extracted according to predefined forms. Heterogeneity within the available evidence will determine the type of evidence synthesis that is appropriate. Findings will be summarized in tables, graphical displays and in a narrative synthesis of the available evidences. A meta-analysis will be carried out if subgroups of studies homogeneous in terms of exposure characteristics, endpoint, and cell types will be identified.

Risk of bias

The internal validity of included studies will be assessed using the NTP-OHAT Risk of Bias Rating Tool for animal studies, adapted to in vitro studies. This stage of the process will be managed through the Health Assessment Workspace Collaborative (HAWC).

Evidence appraisal

To rate confidence in the body of evidence, we will use the OHAT GRADE-based approach for animal studies.

Framework and funding

This protocol concerns one of the evidence streams considered in a larger systematic review of the scientific literature on the potential carcinogenicity of RF-EMF, performed by scientists from several Italian public research agencies. The project is supported by the Italian Workers’ Compensation Authority (INAIL) in the framework of the CRA with the Istituto Superiore di Sanità “BRiC 2018/06 – Scientific evidence on the carcinogenicity of radiofrequency electromagnetic fields”.

中文翻译：

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射频电磁场的遗传毒性：体外研究的系统综述方案

背景

无线通信技术所辐射的射频电磁场（RF-EMF，100 kHz – 300 GHz）是普遍存在的。人们对可能对人体健康的不利影响引起关注。2011年，国际癌症研究机构已将RF-EMF归类为可能对人类致癌的物质，并着重指出证据不足且远没有结论。缺少有关该主题的科学文献的最新系统综述，尤其是对于机械研究而言。

目标

要开发协议以进行系统的实验研究综述，以研究RF-EMF在体外细胞模型中引起的遗传毒性作用。遗传毒性是致癌性的关键生物学指标之一，并且是已确定致癌物的最普遍特征。进行系统审查的预定义程序概述如下。

方法

我们将遵循由国家毒理学计划办公室健康评估和翻译（NTP-OHAT）制定的准则，以适应体外研究的评估。

资格标准

我们将包括实验性体外研究，这些研究仅涉及对RF-EMF的受控暴露与仅在哺乳动物细胞中的遗传毒性之间的关系。纳入的资格将进一步限于同行评审的文章，这些文章报告了基础研究的发现。

信息来源

我们将搜索科学文献数据库NCBI PubMed，Web of Science和EMF-Portal。发布日期将不应用任何过滤器。仅考虑以英文发表的研究。将对所包括论文的参考清单和可用评论进行筛选，以查找未识别的相关论文。引用将通过Endnote X9软件进行管理。

数据提取和结果综合

来自包含论文的数据将根据预定义的形式提取。现有证据中的异质性将决定适当的证据综合类型。调查结果将汇总在表格，图形显示以及可用证据的叙述性综合中。如果将确定在暴露特征，终点和细胞类型方面均一的研究亚组，则将进行荟萃分析。

偏见风险

纳入研究的内部有效性将使用适用于体外研究的NTP-OHAT动物偏倚风险评估工具进行评估。该过程的此阶段将通过健康评估工作区协作（HAWC）进行管理。

证据鉴定

为了评估对证据主体的信心，我们将使用基于OHAT GRADE的方法进行动物研究。

框架和资金

该协议涉及由意大利多家公共研究机构的科学家进行的有关RF-EMF潜在致癌性的科学文献的较大系统综述中考虑的证据流之一。该项目得到意大利工人赔偿局（INAIL）在CRA框架下与SanitàIstituto Superiore diSanità的支持，即“ BRiC 2018/06 –射频电磁场致癌性的科学证据”。