Exposure to radiofrequency radiation increases the risk of breast cancer: A systematic review and meta-analysis.

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). Copyright: © Shih et al.

Introduction

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 (1). Exposure to ionizing radiation has been demonstrated to constitute a breast cancer risk, and primarily is owed to exposure to diagnostic (x-ray) or therapeutic (radiotherapy) sources, outer space (for example, flight crews), radon gas emanating from rocks in the earth and Japanese atomic bombs (1). Non-ionizing radiation is classified into three categories: Extremely low-frequency (1-100 Hz), radiofrequency (100 kHz-3 GHz) and microwave radiation (>3 GHz) (2). Radiofrequency radiation, which is a subcategory of non-ionizing radiation, has been indicated to exhibit harmful effects that are similar to those of ionizing radiation, and to increase the risk of cancer (3).

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 (2). All wireless technologies emit radiofrequency radiation, and certain studies have documented their adverse health effects, and particularly their contribution to increased cancer risk (2,4). Furthermore, in 2011 the International Agency for Research on Cancer (5), which is a branch of the World Health Organization, classified non-ionizing radiofrequency radiation as possibly carcinogenic to humans categorizing it in group 2B (6).

Breast cancer is one of the most commonly diagnosed cancers affecting women in Taiwan, and its incidence rate is gradually increasing worldwide (7). The known risk factors for breast cancer are obesity (8), smoking (9), genetic mutations such as breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene2 (BRCA2) which are tumor suppressor genes (9,10), family history (11,12), alcohol consumption (11-14), exposure to estrogen hormones over an extended period (11,14), diethylstilbestrol and post-menopausal hormone therapy (15,16). In addition, previous studies suggested that breast cancer can be attributed to exposure to radiofrequency radiation (17,18). Experimental research has demonstrated that simulated radiofrequency radiation exposure can cause damage to human breast cancer MCF-7 cells and promote the formation of reactive oxygen species (ROS), which are the primary cause of DNA strand breaks and cell death (17,18). Cigand Naziroglu (17) indicated that exposure of breast cancer cells to radiofrequency radiation was associated with the accumulation of ROS and disruption of mitochondrial membrane pores, which resulted in swelling and dysfunction of mitochondria, causing rupture of the outer membranes and the release of apoptosis-inducing factors. Therefore, it was hypothesized that exposure to radiofrequency radiation may induce breast cancer development due to the induction of oxidative stress and apoptosis in breast cancer cells.

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 (3,6,19,20). Although a number of studies have investigated the association between exposure to radiation and cancer, the majority of meta-analysis studies have focused on the association between mobile phones and tumors (21-23) or electromagnetic fields and breast cancer (24). Potential breast cancer risks from radiofrequency radiation emitted from novel technologies developed last decade, such as digital mobile phones, increases public health concerns (25). Therefore, to the best of our knowledge, the present study performed the first meta-analysis aiming to evaluate and obtain more precise and comprehensive estimates of the association between radiofrequency radiation exposure and the risk of breast cancer.

Materials and methods

Data sources and search strategy

Studies were identified using a comprehensive literature search in the following electronic databases: PubMed (https://www.ncbi.nlm.nih.gov/), Embase (https://www.embase.com/), Cochrane Library (https://www.cochranelibrary.com/), Ovid MEDLINE (http://ovidsp.dc2.ovid.com/sp-4.07.0b/ovidweb.cgi), CINAHL Plus (https://www.ebsco.com/products/research-databases/academic-search-ultimate), Web of Science (http://apps.webofknowledge.com), Airiti Library (http://www.airitilibrary.com/), Networked Digital Library of Theses and Dissertations (http://search.ndltd.org) and ProQuest (https://search.proquest.com), until May 2020. Search terms, including ‘radiofrequency’, ‘radio’, ‘smartphone’, ‘cell phone’, ‘mobile phone’, ‘transmitter station’, ‘antenna’, ‘base station’, ‘radar installation’, ‘Wi-Fi’, ‘breast cancer incidence’ and‘breast neoplasm incidence’ were applied for each database. To increase the precision and specificity of article retrieval, [mesh term] and [text word] were used to search each databases. However, since the Embase database does not have mesh term set up, therefore, we ‘emtree term’/‘exploded’ was used instead of mesh term. If the database does not have mesh term or text word set up, then [keyword] was utilized for searching.

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)].

Inclusion and exclusion criteria

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.

Data extraction

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).

Methodological assessment

A quality assessment method for case and control studies was developed based on the Newcastle-Ottawa Scale (NOS) (26). According to this method, three aspects of all studies were assessed, which included eight indicators for selecting cases and controls, the comparability of cases and controls and the exposure or outcome assessment. The total possible scores ranged from 0-9 points, where a higher scores indicate higher quality. NOS was used to assess the quality of all eight included studies, and the scores of all selected studies ranged between 5-7. A total of three parameters were assessed: i) Selection bias; ii) comparability of the included studies; and iii) assessment of exposure for cohort and case control studies. A total of two investigators individually evaluated the quality of the studies. Any conflicts were resolved by discussion with a third investigator until a consensus was reached.

Statistical analysis

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 (27), when the disease incidence is low (<10%) in unexposed and exposed groups in case-control studies, the OR approximately equals the RR. Therefore, the significance of the RR and 95% CI was examined to determine whether an association between radiofrequency radiation and the risk of breast cancer existed.

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 (28). According to the statistical heterogeneity, fixed-effect models were performed when homogeneity existed.

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 (29), and an Egger's regression test <0.05 indicated publication bias. The trim-and-fill method (30) was used to additionally adjust for the possible bias in the overall log or via imputing the estimated number of missing studies. All statistical tests were two-sided. To estimate the robustness of the findings with respect to different assumptions, a sensitivity analysis was conducted via deleting one study to examine the influence of individual datasets on the pooled RR. All data analyses were performed with Comprehensive Meta-Analysis v2.0 software (Biostats, Inc.).

Results

Study selection

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 Fig. 1. The full manuscripts of 35 articles were obtained, 27 of which were excluded, as 25 studies referred to different target populations, and two studies contained no extractable data. Therefore, eight studies were eligible and were included in the quantitative synthesis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (31) flow diagram of the review process is presented in Fig. 1.

Figure 1

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.

Characteristics of the included studies

The characteristics of the included studies are presented in Table I. The papers were published between 1996 and 2013. A total of four out of eight were cohort studies (32-35), and the other four were case-control studies (36-39). A total of four studies were performed in Northern European countries (Norway and Sweden), two in Israel, one in Turkey and one in Korea. A total of four studies involved occupational exposure to radiofrequency fields, two other studies focused on the residential exposure to radiofrequency fields by people who lived close to antenna/radio transmitters and the remaining two studies examined the use of electrical appliances, including mobile phones/computers. A total of three studies evaluated an age group of ≥50 years old. Subgroup analyses was based on the aforementioned data that were provided by the original research.

Table I

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 et al, 1996	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	(32)
Kliukiene et al, 1999	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	(33)
Pollán et al, 2001	Sweden	203/1,779,646	Cohort	Occupation, occupational title codes	Age, period and geographical area	RR, 1.31; 95% CI, 0.94-1.81	(34)
Ha et al, 2003	Korea	3,152/ 126,523 person-years	Case-control study	Residence, radio transmitters	Age	RR, 1.20; 95% CI, 1.1-1.3	(36)
Kliukiene et al, 2003	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	(37)
Beniashvil et al, 2005	Israel	360/585	Cohort	Electric devices, exposure to mobile phones, televisions and computers	Age	OR, 2.48; 95% CI, 1.35-4.54	(35)
Atzmon et al, 2012	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	(38)
Aydoǧan et al, 2013	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	(39)

RR, relative risk; OR, odds ratio; CI, confidence interval; ER, estrogen receptor.

Methodological quality

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 (35,36,39). These studies either exhibited low response and follow-up rates, particularly with no description of the lack of follow-up and without a precise description of the sample selection, or the study's representability was questioned. The scoring details are presented in Table II.

Table II

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[a]	(Refs.)
Kliukiene et al, 2003	1	1	0	1	2	1	1	0	6	(37)
Ha et al, 2003	1	1	1	0	2	0	0	0	5	(36)
Atzmon et al,2012	1	0	0	1	2	1	1	0	6	(38)
Aydoǧan et al, 2013	1	1	1	0	1	0	1	0	5	(39)
Tynes et al, 1996	1	1	1	0	2	1	1	0	7	(32)
Kliukiene et al, 1999	1	1	1	0	1	1	1	1	7	(33)
Pollán et al, 2001	1	1	1	0	2	1	1	0	7	(34)
Beniashvili et al, 2005	1	1	0	0	1	1	1	0	5	(35)

aThe total possible score ranged from 0-9 points, where a higher score represented a higher quality.

Outcomes of the meta-analysis

The association between radiofrequency radiation exposure and the risk of breast cancer was significant (Fig. 2; pooled RR=1.189; 95% CI, 1.056-1.339). Heterogeneity among the studies was evident (Q=17.6; P=0.014; I2=60%). To estimate how the robustness of the findings affected the final results, a sensitivity analysis was conducted by removing one study (32) from the analysis to detect the pooled RR estimates (RR=1.164; 95% CI, 1.049-1.291) in the random-effects model (Q=13.04; P=0.04; I2=54%), which indicated that the results were statistically robust with only a slight heterogeneity being present.

Figure 2

Forest plot of the overall effect of the association of radiofrequency exposure with the risk of breast cancer.

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 (Fig. 3; RR=2.179; 95% CI, 1.260-3.770), but not among subjects aged <50 years (Fig. 4; RR=1.053; 95% CI, 0.910-1.218). In addition, mobile phone/computer exposure significantly increased the risk of breast cancer (Fig. 5; RR=2.057; 95% CI, 1.272-3.327), but a significant association was not observed for radiofrequency radiation exposure in an occupational environment (Fig. 6; RR=1.274; 95% CI, 0.956-1.697) or for transmitter exposure (Fig. 7; RR=1.133; 95% CI, 0.987-1.300).

Figure 3

Meta-analysis of radiofrequency exposure and the risk of breast cancer among women aged ≥50 years. The subgroup analyses were based on age groups.

Figure 4

Meta-analysis of radiofrequency exposure and the risk of breast cancer among women aged <50 years.

Figure 5

Meta-analysis of radiofrequency exposure to mobile phones and the breast cancer risk.

Figure 6

Meta-analysis of radiofrequency exposure in occupational environments and the breast cancer risk.

Figure 7

Meta-analysis of radiofrequency exposure to transmitters and the breast cancer risk.

Publication bias

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 (Fig. 8).

Figure 8

Funnel plot of the radiofrequency exposure papers included in the meta-analysis. The visual inspection of the funnel plot indicated a slightly substantial asymmetry.

Discussion

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 (40), which are the primary causes of DNA strand breaks that result in cell death (15,40,41). Although it has been indicated that non-ionizing radiation exhibits in sufficient energy to cause DNA strand breaks, the primary cause of DNA strand breaks is considered to be a by-product of ROS metabolism and not high-energy radiation (42-44). A number of in vitro studies have demonstrated an association between radiofrequency exposure and ROS production, resulting in DNA single- and double-strand breaks (42-44).

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 (45,46). Carcinogenic risks following radiation exposure have been revealed to increase with age and enhance the risk of cell inflammation and the loss of oxidant/antioxidant equilibrium (47,48). Age is one of the risk factors that has been associated with breast cancer in women, particularly those exposed to radiation (49). The results of the present study are in accordance with those of a previous study, which reported that radiologic technologists of an older age who worked in an environment with radiation exhibited a higher lifetime attributable risk of breast cancer compared with that in other occupational groups, including radiologists, dentists and nurses (49).

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 (50). In addition, participants who regularly carried their mobile phones close to their breast area for a period of up to 10 h a day were found to be at higher susceptibility of developing tumors on their breasts (50). Richter et al (51) indicated that exposure to a radiofrequency environment increased the risk of developing tumors in various organs, and that long-time and direct exposure to radiation affected the body with a chronic adverse influence on health. When using a mobile phone, a close distance between the phone and the breasts exists, and the breasts are exposed to significant amounts of radiofrequency radiation, which contributes to DNA damage and promotes the development of breast cancer (3). In addition, it has been reported that melatonin is a hydroxyl radical scavenger, and decreased expression of melatonin has been indicated to enhance the oxidative damage and increase breast cancer risk (52). Chang et al (53), conducted a randomized controlled trial to estimate the effect of iPad notebooks on melatonin expression. Their results indicated that electronic devices such as iPads delayed the onset of expression and suppressed the level of melatonin (53). Therefore, the radiofrequency emitted by mobile phones or electronic devices can induce both DNA damage and the suppression of melatonin expression. Suppression of the production of melatonin may cause an increased production of estrogen, resulting in a subsequent increase in the risk of breast cancer (25,52,53).

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 (24,54). However, in the subgroup analysis of the current study, occupational radiofrequency exposure did not exhibit a significant association with breast cancer. This finding is supported by the study of Koeman et al (55), which indicated that in a Dutch cohort study occupational radiation exposure was associated with haemato-lymphoproliferative malignancies, leukemia and non-Hodgkin's lymphoma, but not with breast cancer (adjusted hazard ratio=1.07; 95% CI, 0.94-1.23). Moreover, McElroy et al (56) investigated the breast cancer risk in women who were occupationally exposed to radiation environments, and radiation exposure was differentiated into three categories: Low, medium and high exposure. The ORs were 1.06 (95% CI, 0.99-1.14) for low, 1.09 (95% CI, 0.96-1.23) for medium and 1.16 (95% CI, 0.90-1.50) for high exposure. The results indicated that the risk of breast cancer was not significantly associated with occupational radiation environments, which is consistent with the current study (56). By contrast, a meta-analysis, which comprised of 23 studies, suggested that women who worked in an environment with electromagnetic radiation exhibited an increased risk of breast cancer development (OR=1.07; 95% CI, 1.02-1.13) (15).

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 (55). An actual effect may be overlooked due to a non-differential misclassification of exposure (55). In addition, the exposure definitions using common job codes/titles may be inaccurate (15,56). For example, electronic technicians exposed to radiofrequency radiation may also be exposed to polycyclic aromatic hydrocarbons (PAHs), which are known to increase the risk of breast cancer (56,57).

During the previous few decades, >1.5 million transmitters (radio, television and mobile phone base stations) have been installed around the world (2). A European ecological study, which surveyed 23 different European countries for cancer incidence, examined living residences and the density of frequency modulation (FM) broadcasting transmitters in various regions (19). The incidence of melanoma and breast cancer in the surveyed countries were found to be associated with their respective average densities of transmitters (19). Melanoma and breast cancer exhibited an important association with the density of FM broadcasting transmitters in the European countries examined (19). In the present study, however, no significant association was observed between a close residency to a transmission station and the development of breast cancer. The results of the current study are in accordance with those of Atzmon et al (38), who conducted a population-based case-control study, which included 260 controls and 47 patients with different types of cancers, who were diagnosed between 1989 and 2007. The determination of exposure has been based on the distance of each house to radiofrequency antennas, and a lack of association has been demonstrated between distance of the house to radiofrequency antennas and the incidence rates of breast cancer (OR=1.04; 95% CI, 0.89-1.20) or other cancers (OR=1.00; 95% CI, 0.99-1.02) (38). The lack of association has been attributed to the low radiofrequency levels emitted by the transmitters, resulting in a non-direct exposure of the individuals.

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.