The incidence of primary brain tumors has increased in many countries worldwide [56,57] and gliomas are the most frequent primary brain tumors in adults [58]. Residential exposure during childhood to EMF produced inconsistent results and a lack of an association when related to brain cancers, regardless of the exposure metrics that were used whether based on wire codes, distance, or the measured or calculated fields [59]. When focusing on the health effects, the most studied sources of ELF MF are power lines. Exposure to ELF MF that is emitted by power lines can be assessed by direct methods that rely on measurements at a given place over a time range [60] or by individual monitoring through measuring ELF MF exposures throughout the day by wearable dosimeters [61]. Both methods give little or no information on historical exposure to ELF MF. Indirect methods include geographical information system (GIS) which have been used along with declarative data, such as residential history, to assess residential ELF MF exposure in the general population [62,63,64,65]. Case-control studies that are based on death certificates revealed an association between adult brain tumor mortality and living less than 50 m (odd ratios, OR 1.10 95%, CI 0.74–1.64) [66] or 100 m (OR 2.99, 95%, CI 0.86–10.40) [67] from power lines. In a recent work, significant associations were found between the cumulated duration living at <50 m to high voltage lines (50/60 Hz, 0.3 μT) and all brain tumors (OR 2.94; 95%CI 1.28–6.75) and glioma (OR 4.96; 95%CI 1.56–15.77) [65], confirming previous studies [35,66,67,68,69]. Contrasting results have been reported for brain tumors in children. In childhood brain cancer, with the exception of the possibility of a moderate risk increase in high cut-point analyses (0.3/0.4 µT), no increased risk was evident for different exposure metrics [70,71], whereas children whose MF exposure level was above 0.3 or 0.4 μT, an elevated risk of brain tumor was observed [72,73,74]. In residential areas, the transient electric and MFs would induce higher current density in the child‘s body than power frequency fields with similar field strength [75]. In some studies, there is no evidence for a role of ELF cellphone EMFs in childhood brain cancer [27].

Breast cancer threatens women with the highest incidence and second highest mortality rate of all cancers and in women aged 65 and older when nearly one half of all new breast cancer is diagnosed [76]. The excessive exposure to MFs increases the risk of female breast cancer, as demonstrated in several pooled or meta-analyses as well as subsequent peer-reviewed studies [69]. It is questionable whether chronic human exposure to MFs might affect melatonin secretion, its circadian rhythm, or both [77,78,79,80]. In general, no cumulative effects on melatonin secretion in humans have been found in response to MFs and this rebuts the “melatonin hypothesis” in which a decrease in plasma melatonin concentration (or a disruption in its secretion) would be correlated with the occurrence of breast cancers as a consequence of exposure to MFs [81,82,83,84,85,86,87,88]. Indeed, MF exposure correlates with an increased proliferative activity of the mammary epithelium, which is a likely explanation for the cocarcinogenic or tumor-promoting effects of MF exposure that is observed [89]. However, some authors found a motivation for going back to the melatonin hypothesis in relation to data, suggesting magnetosensory disruption by ELF MF in mammals, and magnetosensitivity in humans, along with the influence of MFs on circadian rhythmicity with a consequent disruption of non-photic sensory stimuli of various nature [90].

In studies that were based on the measurement of an electric bedding device, only premenopausal breast cancer (OR = 1.23; 95% Cl: 1.01, 1.49, p = 0.04) showed a slight increased risk [91]. Breast cancer was found to increase with the number of years and seasons of bedding device use during sleep. Similar trends in dose response were shown in both premenopausal and postmenopausal women and for both estrogen receptor-positive and estrogen receptor-negative tumors. Therefore, there is a growing body of evidence that the use of electric bedding devices may increase breast cancer risk [92]. In terms of geographic variation of breast cancer rates, the results are inconclusive and do not support a major role of MF risk factors in the etiology of breast cancer [93].

Leukemia is the most common cancer in children [94]. The analysis of reports on childhood leukemia as related to exposure to MFs shows that a statistically significant association between MF exposure and childhood leukemia is found in almost all government or independent studies with an elevated risk of at least OR = 1.5, while a not significant or even suggestive association is reported in many industry supported studies [69].

Several meta-analyses showed a statistical association between childhood leukemia and a range of exposure 0.1–2.36 µT MF intensity [74,95,96,97,98,99]. Children that are exposed to elevated ELF-MF show relative risks of leukemia between 1.3 and 2 [100,101,102] and the highest exposure was associated with an increased risk of B-lineage acute lymphoblastic leukemia (B-ALL) when compared with lower exposures [103]. A significant association was observed during the night (OR = 3.21, 95% CI 1.33–7.80) between childhood leukemia and MF exposure [104].

Several epidemiologic case-control studies examined the association between childhood cancer risk and distance to high-voltage overhead transmission lines (HVOTL). Statewide, record-based case-control studies of childhood leukemia evidenced the occurrence of risk that was associated with greater exposure to MF that was generated in areas that were close to power lines [66,105,106,107,108]. Living in polluted regions and pre- and post-natal exposure to high voltage power lines has been described as risk factors of acute lymphoblastic leukemia (ALL) in people of low socioeconomic status Iranian population [109]. In children with ALL, ELF MF-exposure was found to have no impact on the survival probability or risk of relapse [110].

The occurrence of childhood acute leukemia (AL) has been studied around nuclear power plants (NPP). The results suggest a possible excess risk of AL in the close vicinity to NPP [111]. The small, but statistically significant increased incidence of AL in the surrounding of some NPP have motivated governments to work toward a better understanding of the main causes of AL long-term strategic research agendas through interdisciplinary and international efforts [112].

MFs are not the only factor that varies in the vicinity of MF sources, complicating interpretation of any associations. Several reports demonstrate that MFs that are generated by different sources are not an important cause of leukemia both in adults [37,113,114] and children in many geographical areas [12,113,114,115,116,117,118,119,120]. Moreover, exposure levels in some big cities are always significantly far lower than 0.3–0.4 µT [121].

The associations that were observed between power lines exposure and childhood leukemia appears to be not related to mobility [122,123]. No indications were also found of an association of risk for people that are exposed to magnetic fields from underground [124] and above ground lines [106,107] or of a trend in risk with increasing MF for leukemia. Residential proximity to transformer stations has been associated with a borderline risk of childhood cancer [125].

Distance from HVOTLs during the year of birth is unlikely to be associated with an increased risk of leukemia [73] and little evidence was found between exposure to MF inside infant incubators and increased risk of childhood leukemia [126]. No statistically significant association was observed between wire codes and childhood leukemia [127]. Recently, a synoptic analysis provided evidence that the risk of childhood leukemia is not increased by exposure to ELF EMFs, suggesting that IARC’s classification of ELF EMF needs revision [128].

By considering both significant and not significant correlations between MF and leukemia, no major environmental risk factors (including MFs) have been established as major contributors to the global leukemia burden, although distinct incidence patterns by geography, age, and sex suggest a role of the environment in its etiology [129]. The results may be affected by several sources of bias: analyses that are based on continuous exposure show no exposure-disease association, while incoherent exposure-outcome relationships characterize analyses that are based on categorical variables [130].

EMF in the home-environment (color tv, computer monitor, microwave-oven, cellular phone, etc.) might act as potential contributing factors for the development of cancer, as well as exert indirect effects on humans. Microwave exposure induces L-amino acids change to D-amino acids, and exposure of the human body to microwaves over a long period of time may contribute to induction of cancer [131]. Exposure to EMF that is generated by electric blankets has been suggested to increase the risk of hormone-dependent cancers such as testicular [132] and prostatic [133], but was not significantly associated with endometrial cancer risk [134]. MFs of industrial frequency have been shown to be a risk factor for occurrence of oncological diseases in the population and an increased incidence of malignant tumors has been noted as the induction of the magnetic field that is produced by HVOTL increases [135]. The incidence of melanoma has been linked to the distance to FM broadcasting towers. A correlation between melanoma incidence and the number of locally receivable FM transmitters was found when geographic differences in melanoma incidences were compared with the magnitude of this environmental stress. Therefore, melanoma might be associated with exposure to FM broadcasting [136]. By considering pregnancy duration, neonatal birth weight, length, head circumference, gender, and con-genital malformations, no significant effects of ELF EMFs were observed; however, precautionary measures are necessary to reduce exposure to EMFs by pregnant women [137].

The Supplementary Table S1 reports the relationship between MFs and cancer in epidemiologic studies that are related to domestic/residential exposure to MFs. The type of cancer, study design, source of MF, range of MF exposure, location of the epidemiologic study, and the main conclusions are reported. Figure 2 summarizes the epidemiology of residential/domestic exposure to MF.

Occupational exposure to ELF EMF is a suspected risk factor for brain tumors; however, the literature reports contrasting results. In adults, some meta-analyses of occupational studies indicate a slightly higher risk for electrical workers, suggesting a small increase in brain cancer risk [61,144,145], including childhood brain tumors [146], while others found no evidence to support the hypothesis that exposure to MFs is a risk factor for gliomas or meningiomas [147,148,149,150].

Several studies have evaluated the evidence linking women’s occupation and workplace exposures to breast cancer. Overall, the data do not suggest that occupational exposures to EMF increases the risk of breast cancer [144,145,151,152] with some exceptions [153]. Some studies have found an effect when looking at overall risk elevations in the women studied [154] with increased risk among postmenopausal women but not premenopausal women [155]. The hypothesis that daytime occupational exposure to MF enhances the effects of nighttime light exposure on melatonin production (see above the “melatonin hypothesis”) has been provided [153]. Occupational MF exposure has also been suggested as a risk factor for breast cancer in men. An elevated risk of breast cancer was found in men who were exposed to 0.6 T when compared to those with exposures <0.3 T; however, large case-control studies of breast cancer in men that have been conducted to date provide limited support for the hypothesis that exposure to MF increases the risk breast cancer in men [156].

Epidemiological studies addressing occupational ELF MF exposure and risk of leukemia in adults have yielded slightly increased risks in exposed workers. Some studies show a positive correlation between occupational MF and leukemias [157,158,159,160] and have suggested that stronger effects may be observed for acute myeloid leukemia (AML) [161,162], chronic myeloid leukemia (CML), ALL [138], lymphatic leukemia (LL) [163], and for chronic lymphocytic leukemia (CLL) [162]. In general, however, no clear exposure-response pattern has emerged from the studies that evaluated exposure levels and some results do not support an association between occupational ELF MF or electric shock exposure and AML [164].

Differences between the study designs or the populations that were studied might be the cause of lack of consistency regarding the type of leukemia that is associated with MF exposure, and still no firm conclusions can generally be drawn based on the existing evidence [165,166,167]. No association was found between childhood leukemia risk and parental occupational exposure to ELF EMF [168,169,170].

In men, exposure to EMF showed an increased incidence of tumors of the liver, biliary passages, kidney, and pituitary gland; for these cancer sites an exposure-response relation was indicated [171]. There was very limited evidence for associations between occupational ionizing radiation and testicular cancer, while there were some positive associations for EMF [172].

Women that were exposed to MF showed an increased incidence of astrocytoma I-IV, for cancer of the corpus uteri and multiple myeloma, with a clear exposure-response pattern [171].

For both men and women, there was weak support for the hypothesis that occupational MFs exposure increased the risk of non-Hodgkin lymphoma [173], acoustic neuroma [174,175], and thyroid cancer [176], while sources that produce ELF fields were not associated with neuroblastoma in offspring [177].

MF has previously been associated with mortality from acute myocardial infarction (AMI) and arrhythmia but not from chronic coronary heart disease (CCHD) or atherosclerosis in electric utility workers. For cumulative exposure, no association was observed with mortality from AMI or CCHD, indicating no exposure-related risk increase for AMI mortality, which does not confirm previous results [178].

Supplementary Table S2 reports the relationship between MFs and cancer in epidemiologic studies that are related to the occupational exposure to MFs. The type of cancer, study design, source of MF and occupation, range of MF exposure, location of the epidemiological study, and the main conclusions are reported. Figure 3 summarizes the epidemiology of occupational exposure to MF.

Several studies revealed that there were not significant effects of MF on cancer in mouse studies, failing to support the hypothesis that acute MF exposure causes DNA damage. The experimental mice were injected with mammary murine adenocarcinoma to investigate the interaction between a 50 Hz, 2 mT MF exposure and cell growth.

Neither the time of tumor cell injection nor the time of exposure produced differences between the unexposed, sham, and exposed mice [231] and no association between exposure and the incidence of benign or malignant tumors was found in squamous cell carcinomas of mice that were exposed to 60 Hz, 2 mT [232]. Also, the results do not support the hypothesis that acute MF exposure causes DNA damage and apoptosis in the cerebellums of immature mice that were exposed to 60 Hz and 1 mT for 2 h [233,234].

Exposure to 50 Hz and 500 µT MF did not alter responses of inflammatory genes and the activation of splenic lymphocytes in mice [235] and was not a significant risk factor for hematopoietic diseases, even when high exposure levels were used (50 Hz, 1 mT for 7 days) [236]. In mice, as revealed in humans (see above), long-term and continuous exposure to simulated powerline MFs (0.5–77 µT) did not result in a decreased nocturnal melatonin secretion [85].

The use of NI MFs has shown early promise in a number of animal studies as an effective tool against many types of cancer (see also below). The effect of varying durations of MF exposure on tumor growth and viability has been studied in mice that were injected with breast cancer cells by using an in vivo imaging system. The results showed the potential of MF in cancer therapeutics, either as adjunct or primary therapy [237].

Long-term exposure showed a significant effect of MF on mice. When a parental generation of six week-old OF1 mice was exposed to an artificial ELF MF (50 Hz, 15 µT) for 14 weeks, activated partial thromboplastin time and reptilase time values significantly increased in the female mice, which also showed a very significant shortening of the prothrombin time that was associated with ELF MF exposure [238]. A chronic exposure of mice to a 60 Hz and 110 µT intensity was found to influence some hematologic parameters and the weight of thee liver and also caused spleen hyperfunction [239]. Long-term exposure to MF (50 Hz, 50 µT) was found to be a significant risk factor for neoplastic development and fertility in C57BL/6NJ female mice and C3H/HeNJ male mice [240].

Both positive and negative effects of MF have been demonstrated in studies using rats. Artificial MFs of 1 mT that was administered for seven weeks was not carcinogenic nor cancer-promoting for colon carcinogenesis in male Sprague–Dawley rats [241]. No overall effects of 60 Hz and 1 mT MF on splenomegaly or survival were found in the exposed Fischer/344 rats. In addition, no significant and/or consistent differences were detected in the hematological parameters between the exposed and control rats [242]. MF exposure for 14 weeks to 6.45 µT did not appear to be a strong co-tumorigenic agent in Sprague–Dawley female rats mammary, lung, and skin models [243]. On the other hand, EMFs resulted in significant alterations in cell adhesion mechanisms when histological, immunohistochemical, and histopathological analyses were performed on Wistar albino rats that were exposed for six months to 5 mT MFs [244]. MF exposure (50 Hz, 100 µT for 2–26 weeks) of female Sprague–Dawley rats resulted in an increased proliferative activity of the mammary epithelium which was associated with the cocarcinogenic or tumor-promoting effects of MF exposure that was observed in the 7,12-dimethylbenz(a)anthracene model of breast cancer [89], and mammary tumorigenesis [245].

The Supplementary Table S4 reports the effects of MFs on both mice and rats. The type of cell, response to MF, range and duration of MF exposure, materials and methods used, and the main conclusions are reported. Figure 4 summarizes the in vivo and in vitro effects of magnetic fields on cancer from studies on human cells (including cell-free systems) and in animals (mice and rat).