Research into the health effects of radiofrequency radiation (RFR) has lagged the rapid growth in use of communication technologies based on this part of the electromagnetic spectrum. 1–3 Existing safety standards are intended to provide protection from thermal effects, such as burns and cataracts, which are associated with acute, high-dose exposures. 1,2 Such exposures are uncommon in the general population, in contrast to the chronic, low dose-rate exposures experienced by a large and growing segment of the public, namely, users of cellular (mobile) telephones. Whether there are any health risks associated with non-thermal, low dose-rate exposures, apart from interference with medical devices, 4 is unknown. Given the pervasiveness of cell phone use, even small health risks would be of considerable public health importance. Of all of the hypothesized adverse effects of RFR, cancer has elicited the greatest concern. Interest has centered on tumors of the brain and nervous system and hematopoietic and lymphatic tissue. 2,3,5–7 The paper by Stang and colleagues 8 in this issue is unusual in its focus on uveal (intraocular) melanoma, the most common type of eye cancer among adults. 9 The authors report elevated relative risk estimates associated with a history of employment in occupations involving use of selected RFR transmitting devices, including cellular telephones and portable, two-way radios. Of interest here is the strength of the evidence that the association is causal.
Radiofrequency radiation (300 Hz-300 GHz), including microwave radiation, encompasses a broad range of frequencies intermediate between extremely low frequency (ELF) fields at the lower end and infrared radiation at the upper end (Figure 1). Solar radiation includes RFR, but at very low power densities, and exposure to RFR is essentially a man-made phenomenon of the past century. 3,10 Sources of exposure include cellular telephones, VHF and UHF two-way radios, cordless phones, AM and FM radio, VHF and UHF television, microwave ovens, magnetic resonance imaging systems, video display terminals, anti-theft devices and security alarms, induction heaters and heat sealers, radar and satellite communications. 1,3,5,6,11 Cellular telephones operate within the 800 to 960 MHz and 1.4 to 2.2 GHz bands, and portable radios operate in several bands, including 450 to 512 MHz. 1,6,12 Frequencies from 806 to 890 MHz formerly were used for UHF TV channels 70 to 83. 1
By way of comparison, the frequency of ultraviolet radiation (UVR) is of the order of 1 to 10 million times higher, and the frequencies of X- and γ-radiations are several orders of magnitude higher still (Figure 1). 1 Because the energy of a photon of radiation is directly proportional to its frequency, the enormous differences in frequency imply similar, orders-of-magnitude variation in the energy of the radiation. 1,10,13 Gamma-rays and X-rays are sufficiently energetic to break chemical bonds and ionize molecules. UVR does not ionize molecules but is energetic enough to cause molecular excitations resulting in structural changes in DNA that can lead to mutations. RFR can induce molecular excitations resulting in tissue heating and, possibly, influence the electrical environment of cells and behavior of free radicals, 14 but it does not damage DNA directly. 10,13,15
Notably missing from the paper by Stang et al. is any consideration of occupational or recreational exposure to UVR. Exposure to UVR is virtually universal, and UVR is a generally accepted cause of cutaneous melanoma. 16,17 Uveal melanoma is considerably less common and less studied than cutaneous melanoma, and there are differences in epidemiologic patterns that might reflect differences in etiology. 18 There are, however, noteworthy similarities as well, and associations between the incidence of ocular melanoma and exposure to UVR have been reported in several studies. 19–24 Sailors, welders and farmers have been reported to be at high risk, and all three groups are potentially exposed to intense or prolonged UVR. 21,25 Exposure to sun lamps and fluorescent lights also has been linked to increased risk, as has a history of nonmelanoma skin cancer, 22 a type of cancer for which the association with UVR is not in dispute. Intermittent, intense exposure, such as that associated with sunburns, appears to be more important than chronic or cumulative exposure, at least for some types of melanoma, and occupational groups at highest risk are not necessarily those who spend the most time outdoors. 16,22,26–28 Overall, the reverse seems to be true, with a higher relative risk associated with indoor work than outdoor work, and with higher rather than lower social class. 29,30
The likely etiologic importance of UVR has been questioned on the grounds that little UVR penetrates the cornea and lens to reach the choroid, where most uveal melanomas arise. 31,32 The lens, however, transmits some long wavelength UVR in adults and a much higher proportion of 300–400 nm UVR in children. 10,33,34 It also is possible that UVR carcinogenicity is mediated through a systemic effect, such as on the immune system. 35–37 Although the role of UVR (or other forms of solar radiation) in the etiology of ocular melanoma is an unsettled issue, UVR is a stronger candidate, on a priori grounds, than RFR or ELF and merits consideration as part of a study concerning the risk of uveal melanoma associated with “... occupational exposures to different sources of electromagnetic radiation ...” [sic] [see Abstract].
As with UVR, the depth of penetration of RFR in tissue varies inversely with frequency. 1,2,5,10 Very high frequency RFR is absorbed almost entirely at the surface of the skin, where it produces heating. Very low frequency RFR penetrates tissue but does not cause heating; instead, it induces electric currents and fields. RFR of the intermediate frequencies used by cellular phones and portable radios is attenuated rapidly with passage through tissue. 6 The level of RFR reaching the highly vascularized choroid would be insufficient to raise temperature above background levels. The mechanism by which non-thermal doses of RFR might cause cancer is unknown. Neither ionizing radiation nor UVR serve as a good model, as both of these established carcinogens are genotoxic, and even brief exposures can pose a risk. A variety of possible non-genotoxic, carcinogenic effects of RFR have been hypothesized, many of which involve potentiation of effects due to other agents. 14
Stang et al. speculate that RF radiation might act as a cancer promoter, by inhibiting melatonin production by cells in the retina and ciliary body, which, in turn, might remove a block to proliferation of potentially cancerous cells. This parallels Stevens’38 hypothesis concerning breast cancer and ELF fields. Nevertheless, exposure to ELF fields was not associated with risk of uveal melanoma in the present study, nor was exposure to video display terminals or radar. The authors do not explain why they would expect RFR associated with use of cellular phones or radio sets to be more effective in suppressing melatonin secretion than ELF fields, visible light, or low or high frequency RFR. The relative importance of melatonin production in the eye (choroid) versus in the pineal gland also is unclear. de Seze et al.39 did not observe evidence of altered melatonin levels in circulating blood associated with use of cellular phones.
Speculation about possible mechanisms seems a bit premature, given the limitations of the study and the lack of corroborative evidence in the literature. The authors note that their study was part of a much larger effort to study risk factors for eight different cancer sites and was not designed to address RFR exposures in particular; hence, the lack of a detailed RFR exposure assessment. Intensity of exposure could not be addressed, and there was no power for assessing either duration of exposure or latency. The overall odds ratio of 3.0 associated with use of radio sets or mobile phones was based on a total of 16 exposed cases. Information was not available concerning domestic use of cellular phones or tumor laterality relative to side of phone use. There are potentially important occupational exposures beyond those considered. 1,5,11,40 Swerdlow 41 observed that “poor measurement both diminishes the capability of studies to determine whether there is an association of RF with risk of disease and, if a raised risk is found, to judge whether the association is causal.”
If Stang et al.’ s hypothesis is correct, and use of a cellular phone increases the risk of uveal melanoma appreciably, then one would expect the incidence to increase over time. Most informative would be data for countries or regions with longer histories of widespread, heavy cellular phone use. Unlike cutaneous melanoma, the incidence of ocular melanoma remained relatively stable during the latter half of the 20th century. 18,42 If there has been a recent increase due to use of cellular phones, it is less likely to be mixed in with a longer term secular trend due to some other factor.
At present, there is no strong reason to believe that RFR causes cancer, but there is only a very limited epidemiologic literature on which to base evaluations. The extent of public exposure and concern requires that the question be investigated further. Stang and colleagues raise the possibility that we should add a new type of cancer to those already under leading consideration as possible hazards of RFR, and it may well be that future studies will support their hypothesis. At this point, however, given the small size of their study, the relatively crude exposure assessment, the absence of attention to UVR exposure or other possible confounding variables, and limited support in the literature, a cautious interpretation of their results is indicated.
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