The present systematic review and meta-analysis investigated the association between exposure to radiofrequency radiation and the risk of breast cancer. The published studies that were available in PubMed, Embase, Cochrane Library, Ovid MEDLINE, CINAHL Plus, Web of Science, Airiti Library, Networked Digital Library of Theses and Dissertations and ProQuest until May 2020 were investigated. A total of eight studies (four case-control and four cohort studies) were eligible for quantitative analysis. A significant association between radiofrequency radiation exposure and breast cancer risk was detected [pooled relative risk (RR)=1.189; 95% confidence interval (CI), 1.056-1.339]. Subgroup analyses indicated that radiofrequency radiation exposure significantly increased the risk of breast cancer susceptibility among subjects aged ≥50 years (RR=2.179; 95% CI, 1.260-3.770). Pooled estimates revealed that the use of electrical appliances, which emit radiofrequency radiation, such as mobile phones and computers, significantly increased breast cancer development (RR=2.057; 95% CI, 1.272-3.327), while occupational radiofrequency exposure and transmitters did not increase breast cancer development (RR=1.274; 95% CI, 0.956-1.697; RR=1.133; 95% CI, 0.987-1.300, respectively). It was concluded that radiofrequency radiation exposure significantly increased the risk of breast cancer, especially in women aged ≥50 years and in individuals who used electric appliances, such as mobile phones and computers. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis, an evaluation protocol was prepared and registered with the PROSPERO database (registration no. CRD42018087283).
Electromagnetic radiation is categorized into two types, ionizing and non-ionizing radiation. Ionizing radiation, which consists of higher frequencies, exhibits sufficient energy to remove electrons from atoms, thereby destroying chemical bonds in molecules (
Radiofrequency radiation is invisible but surrounds living organisms, as it emanates from mobile phones, smart phones, wireless computers, base stations, radios, cellular transmitters and other common Wi-Fi technology sources (
Breast cancer is one of the most commonly diagnosed cancers affecting women in Taiwan, and its incidence rate is gradually increasing worldwide (
In addition, previous studies have also focused on the effects of the exposure to non-ionizing radiofrequencies on brain tumors, leukemia, salivary gland tumors, infertility and electro-hypersensitivity (
Studies were identified using a comprehensive literature search in the following electronic databases: PubMed (
The strategy used for searching PubMed was as follows: [‘Radiofrequency’ (Text Word) OR ‘radiofrequency’ (MeSH Terms) OR ‘radio’ (Text Word) OR ‘radio’ (MeSH Terms) OR ‘smartphone’ (Text Word) OR ‘smartphone’ (MeSH Terms) OR ‘cell phone’ (Text Word) OR ‘cell phone’ (MeSH Terms) OR ‘mobile phone’ (Text Word) OR ‘mobile phone’ (MeSH Terms) OR ‘transmitter station’ (Text Word) OR ‘transmitter station’ (MeSH Terms) OR ‘antenna’ (Text Word) OR ‘antenna’ (MeSH Terms) OR ‘base station’ (Text Word) OR ‘base station’ (MeSH Terms) OR ‘radar installation’ (Text Word) OR ‘radar installation’ (MeSH Terms) OR ‘Wi-Fi’ (Text Word) OR ‘Wi-Fi’ (MeSH Terms)] AND [‘breast cancer incidence’ (Text Word) OR ‘breast cancer incidence’ (MeSH Terms) OR ‘breast neoplasm incidence’ (Text Word) OR ‘breast neoplasm incidence’ (MeSH Terms)].
The title and abstract of all retrieved articles were reviewed. The studies were limited to those involving human individuals and were written either in English or Chinese, but with no limitation on the date in which the study was conducted. For inclusion, the studies were required to meet all the following criteria: i) Evaluated associations between radiofrequency radiation and the risk of breast cancer; ii) studied a human population; iii) provided detailed data for calculating the relative risk (RR) or odds ratio (OR) and 95% confidence interval (CI); and iv) investigated radiofrequency radiation or any frequency classified as radiofrequency. All observational studies (cohort, cross-sectional and case-control studies) were included, the primary outcomes of the incidence rate recorded in the Cancer Registry of breast cancer were examined and detailed data for calculating the RR or OR and 95% CI were provided. A total of two investigators developed the selection criteria and conducted the literature search. Another investigator assessed the retrieved studies for accuracy and reliability of meeting the inclusion criteria, and independently examined the included studies. Studies were excluded if they were; i) duplicates of previous publications; ii) meta-analyses, commentaries, letters, reviews or editorial articles; and iii) were performed in animal models.
Initially, the title and abstract of all articles were reviewed to identify their eligibility by two reviewers, and studies were considered eligible if they investigated the association between radiofrequencies and breast cancer risk. All studies matching the inclusion criteria were retrieved for subsequent examination and data extraction. The rates and the observed and expected cases from candidate studies were validated to ensure that appropriate data were identified and correctly transcribed into a spreadsheet. A total of two investigators developed a data extraction sheet and independently extracted the data from each study, including characteristics of the selected studies (authors' names and year of publication), the patient populations (country and number of patients in each group), the study design (cohort or case-control study design), the exposure to radiation (type, frequency, length and intensity of exposure) and outcome measures and confounding variables of the study. Discrepancies were examined by another investigator and consensus was achieved by discussion between all investigators. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis, an evaluation protocol was prepared and registered with the PROSPERO database (registration no. CRD42018087283).
A quality assessment method for case and control studies was developed based on the Newcastle-Ottawa Scale (NOS) (
All quantitative data were pooled to assess the association between radiofrequency radiation exposure and the risk of breast cancer using the RR. According to Pagano and Gauvreau (
Heterogeneity was examined using the Cochran Q-test and I2 test. A Cochran Q-test score <0.05 and an I2-value of >50% were considered to represent substantial heterogeneity, whereas a Cochran Q-test score ≥0.05 and an I2-value of <50% were considered to represent homogeneity across studies (
Subgroup analyses were conducted to determine the possible influences of certain factors, including age, mobile phones and computers, occupational radiofrequency, transmitters. Funnel plot asymmetry was measured using Egger's regression intercept test (
The search strategy yielded 9,571 studies, and 4,980 studies remained following the removal of duplicates, 4,556 of which were excluded after screening the title and abstract. The reasons for exclusion are presented in
The characteristics of the included studies are presented in
A methodological quality assessment was performed for all included studies using NOS, and the scores of all selected studies ranged from 5-7, with the average score being 6. The lowest score of the included studies was 5 (
The association between radiofrequency radiation exposure and the risk of breast cancer was significant (
The sources of heterogeneity were additionally explored via a subgroup analysis of the age and the different types of radiofrequency radiation exposure sources, according to the previously established characteristics of the studies. The results indicated that radiofrequency radiation exposure significantly increased the risk of breast cancer susceptibility among subjects aged ≥50 years (
The visual inspection of the funnel plot indicated a slightly substantial asymmetry. The funnel plot revealed that two studies were not within the 95% CI, and Egger's regression intercept test also indicated evidence of publication bias among the studies (Egger's test, t=2.46;P=0.048). A subsequent analysis was performed using the trim-and-fill method, which indicated that the adjusted point estimate was 1.121 (95% CI, 1.067-1.177) with four missing studies imputed at the left side of the funnel plot (
In the present study, a meta-analysis of eight studies published between 1996 and 2013 was performed, in order to determine the potential association of radiofrequency radiation exposure with breast cancer. The exposure types that were examined in the present study included exposure to occupational radiofrequency radiation, which comprised female radio/telegraph operators and women employed in the electronics industry, electric appliances, including daily mobile phone and computer use and radio/antenna transmitter exposure in a radiofrequency radiation environment. The current study indicated that there was a significant association between exposure to radiofrequencies and breast cancer risk (pooled RR=1.189; 95% CI, 1.056-1.339). To the best of our knowledge, this is the first meta-analysis that combined studies on radiofrequency to determine an association with the risk of breast cancer. The biological mechanism via which radiofrequency radiation exposure increases the breast cancer risk may be associated with the fact that exposure to radiofrequency radiation has been revealed to result in mammary cell damage and ROS formation (
In the subgroup meta-analyses performed in the present study, the risk of breast cancer was indicated to increase in women aged ≥50 years (RR=2.179; 95% CI, 1.260-3.770). Aging results in a decline in physiological organ function, and it has also been indicated to be a major risk factor for cancer development (
Regarding the exposure type of radiofrequency, subgroup analysis revealed that mobile phone use increased breast cancer risk (RR=2.057; 95% CI, 1.272-3.327). A study consisted of case reports of four young women aged 21-39 years, who exhibited no family history and tested negative for BRCA1 and BRCA2. Their breast imaging was reviewed and demonstrated clusters of multiple tumor foci in the breast directly under the area of phone contact (
Occupational studies have provided evidence of increased cancer risks associated with chemicals in manufacturing (polycyclic aromatic hydrocarbons) and agriculture (pesticides and dichlorodiphenyltrichloroethane), as well as night-shift work, metals and both ionizing and non-ionizing radiation (
Inconsistencies in the conclusions of several studies on occupational radiation exposure may be attributed to the lack of an accurate assessment of occupational radiofrequency field exposure, where exposure classification was regularly solely based on the occupational code/title (
During the previous few decades, >1.5 million transmitters (radio, television and mobile phone base stations) have been installed around the world (
The current study presents certain limitations. Firstly, only results in the selected papers were used, which limited the analyses. The sample size was sufficient for an overall size effect, but the statistical power of certain subgroup analyses may be insufficient. For example, the results of the subgroup analyses on the occupational environment and transmitters were borderline significant, while with a larger sample size, these results may have exhibited a greater statistical power. Secondly, a dose-response relationship was not determined, which was attributed to complicated exposure conditions, numerous exposure assessment methods and inconsistencies in the exposure definitions and the units of exposure calculations. Finally, the quality of the included studies was assessed using NOS. The scores of all selected studies ranged from 5-7 with the average rating being 6, which demonstrated that the quality of these studies was medium to high. A publication bias among the studies was also indicated, which may be attributed to the acceptance and publication of studies that report significant results. Therefore, additional research studies should be conducted, and higher-quality studies are required for future analysis.
In conclusion, the present study indicated that radiofrequency radiation exposure significantly increased the risk of breast cancer, especially in women aged ≥50 years and individuals who used electric appliances, such as mobile phones and computers. Therefore, effective self-protection strategies against radiofrequency radiation require further development.
Not applicable.
The present study was supported by The Ministry of Science and Technology, Taiwan (grant nos. MOST 103-2314-B-040-005-MY3 and MOST 106-2314-B-038-013-MY3).
All data generated or analyzed during this study are included in this published article.
YWS, AO and HTT conceived and designed the study. YWS and CSH collected the data. YWS, WHH and KHC analyzed and interpreted the data. YWS drafted the article. HTT critically revised the article. All authors read and approved the final manuscript.
Not applicable.
Not applicable.
The authors declare that they have no competing interests.
Preferred Reporting Items for Systematic Reviews and Meta-Analyzes flow diagram of the review process. A total of 9,571 studies were searched initially, 4,980 duplicate articles were excluded. A further 4,556 articles were excluded due to the following reasons: Conference papers/editorial letter/comments (n=32); meta-analysis or reviews (n=87); animals/cell/gene studies (n=978); study protocol (n=22); being irrelevant to the main subject, including those that did not focus on exposure and breast cancer incidence, radiation for the treatment of cancers and the prevention of cancer recurrence (n=1,286); being the irrelevant outcome of incidence for breast cancer, such as those investigating radiofrequency and the risk of other cancers except for breast cancer (n=890); and exposure not within scope of study (n=1,261). In total, there were 35 studies remaining for full manuscript review, of which 27 studies were excluded: Different target population (n=25) and data could not be extracted (n=2). Finally, 8 studies were included for further qualitative and quantitative analyses.
Forest plot of the overall effect of the association of radiofrequency exposure with the risk of breast cancer.
Meta-analysis of radiofrequency exposure and the risk of breast cancer among women aged ≥50 years. The subgroup analyses were based on age groups.
Meta-analysis of radiofrequency exposure and the risk of breast cancer among women aged <50 years.
Meta-analysis of radiofrequency exposure to mobile phones and the breast cancer risk.
Meta-analysis of radiofrequency exposure in occupational environments and the breast cancer risk.
Meta-analysis of radiofrequency exposure to transmitters and the breast cancer risk.
Funnel plot of the radiofrequency exposure papers included in the meta-analysis. The visual inspection of the funnel plot indicated a slightly substantial asymmetry.
Characteristics of the included studies (n=8).
First author, year | Country | No. cases/Total population | Study design | Exposure type | Confounder variables | Principal results | (Refs.) |
---|---|---|---|---|---|---|---|
Tynes |
Norway | 50/2,619 | Cohort | Occupation, radio and telegraph operators working at sea | Age and shift | OR 4.6; 95% CI, 1.26-16.68 | ( |
Kliukiene |
Norway | 22,543/21,483,769 person-years | Cohort | Occupation, occupational title codes | Age, socioeconomic status and age at first birth | RR, 1.14; 95% CI, 1.10-1.19 | ( |
Pollán |
Sweden | 203/1,779,646 | Cohort | Occupation, occupational title codes | Age, period and geographical area | RR, 1.31; 95% CI, 0.94-1.81 | ( |
Ha |
Korea | 3,152/ 126,523 person-years | Case-control study | Residence, radio transmitters | Age | RR, 1.20; 95% CI, 1.1-1.3 | ( |
Kliukiene |
Norway | 99/396 | Case-control study | Occupation, radio and telegraph operators at sea | Age and ER status | OR, 1.43; 95% CI, 0.74-2.74 | ( |
Beniashvil |
Israel | 360/585 | Cohort | Electric devices, exposure to mobile phones, televisions and computers | Age | OR, 2.48; 95% CI, 1.35-4.54 | ( |
Atzmon |
Israel | 10/297 | Case-control study | Residence, cellular and radio antenna transmitters | Age, gender, education, smoking, radiation intensity and years | OR, 1.04; 95% CI, 0.89-1.20 | ( |
Aydoǧan |
Turkey | 70/140 | Case-control study | Electric devices, environment and daily mobile phone use | Number of children and stress | OR, 1.50; 95% CI, 0.68-3.29 | ( |
RR, relative risk; OR, odds ratio; CI, confidence interval; ER, estrogen receptor.
Assessment of the included studies quality using the Newcastle-Ottawa Scale (n=8).
Case control study | Selection | Comparability | Exposure | |||||||
---|---|---|---|---|---|---|---|---|---|---|
First author, year | Adequate definition of patient cases | Representability of patient cases | Selection of controls | Definition of controls | Control for important factor or additional factors | Ascertainment of exposure | Same method of ascertainment for participants | Non-response rate | Total score |
(Refs.) |
Kliukiene |
1 | 1 | 0 | 1 | 2 | 1 | 1 | 0 | 6 | ( |
Ha |
1 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 5 | ( |
Atzmon |
1 | 0 | 0 | 1 | 2 | 1 | 1 | 0 | 6 | ( |
Aydoǧan |
1 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 5 | ( |
Tynes |
1 | 1 | 1 | 0 | 2 | 1 | 1 | 0 | 7 | ( |
Kliukiene |
1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 7 | ( |
Pollán |
1 | 1 | 1 | 0 | 2 | 1 | 1 | 0 | 7 | ( |
Beniashvili |
1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 5 | ( |
aThe total possible score ranged from 0-9 points, where a higher score represented a higher quality.