Electromagnetic Biology and Medicine, Early Online: 18, 2012 Copyright Q Informa Healthcare USA, Inc.

ISSN: 1536-8378 print / 1536-8386 online DOI: 10.3109/15368378.2012.701192

Cancer risks related to low-level RF/MW exposures, including cell phones

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Stanislaw Szmigielski
Military Institute of Hygiene and Epidemiology, Warsaw, Poland

For years, radiofrequency (RF) and microwave (MW) radiations have been applied in the modern world. The rapidly increasing use of cellular phones called recent attention to the possible health risks of RF/MW exposures. In 2011, a group of international experts organized by IARC (International Agency for Research on Cancer in Lyon) concluded that RF/MW radiations should be listed as a possible carcinogen (group 2B) for humans. Three meta-analyses of case-control studies have concluded that using cell phones for more than ten years was associated with an increase in the overall risk of developing a brain tumor. The Interphone Study, the largest healthrelated case-control international study of use of cell phones and head and neck tumors, showed no statistically signicant increases in brain cancers related to higher amounts of cell phone use, but excess risk in a small subgroup of more heavily exposed users associated with latency and laterality was reported. So far, the published studies do not show that mobile phones could for sure increase the risk of cancer. This conclusion is based on the lack of a solid biological mechanism, and the fact that brain cancer rates are not going up signicantly. However, all of the studies so far have weaknesses, which make it impossible to entirely rule out a risk. Mobile phones are still a new technology and there is little evidence about effects of long-term use. For this reason, bioelectromagnetic experts advise application of a precautionary resources. It suggests that if people want to use a cell phone, they can choose to minimize their exposure by keeping calls short and preferably using hand-held sets. It also advises discouraging children from making non essential calls as well as also keeping their calls short. Keywords Cancer risks, Carcinogenesis, Radiofrequency/microwave (RF/MW) radiations, Low-level radiation, Cell phones

INTRODUCTION Radiofrequency (RF) and microwave (MW) radiations, defined as part of electromagnetic spectrum at frequencies of 0.1 300,000 MHz are widely used in radio communication, radio location, cellular phones, industry, and households. Absorption of large amounts of RF/MW energy results in development of thermal effects. Many other physical parameters of exposure have been reported to be important for non thermal (specific) biological effects, which are induced by MWs at intensities well below any detectable heating (Baan, 2012; Baan et al., 2011; Belyaev et al., 2000; Jauchem, 2008; Szmigielski and Sobiczewska, 2000; WHO/INIRC, 1993). There are plenty of good, peer-reviewed, scientific reports in the literature showing

Address correspondence to Stanislaw Szmigielski, Military Institute of Hygiene and Epidemiology, 4 Kozielska, 01-163 WARSAW, Poland. E-mail: szmigielski@wihe.waw.pl

S. Szmigielski

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evidence of biological effects that are likely to lead to adverse effects on health and well-being (Baan, 2012; Vargo et al., 2012). According to WHO/ICNIRP Environmental Health Criteria (1993), non thermal intensities of MWs are presently recognized as a weak factor of biological influence. However, after 30 years of research into this area, there is still insufficient information on the specific biological influence of non thermal intensity of RF/MW radiation (Jauchem, 2008). The rapidly increasing use of cell phones (also known as wireless or mobile telephones), which are in fact weak radio stations applied close to the head and switched on to emit GSM-modulated 850 900 or 1800 MHz MWs, recently called attention to possible health risks of RF/MW exposures, including risk of developing neoplastic diseases (Szmigielski and Sobiczewska, 2000). The number of cell phone users has increased rapidly. As of 2010, there were more than 303 million subscribers to cell phone service in the United States. This is a nearly three-fold increase from the 110 million users in 2000. Globally, the number of cell phone subscriptions is estimated to be 5 billion (Vrgo et al., 2012). In view of this, exposure to MWs, both individually and publicly, has increased considerably. Holding a cell phone to the ear to make a voice call can result in high specific absorption-rate (SAR) values in the brain, depending on the design and position of the phone and its antenna in relation to the head, how the phone is held, the anatomy of the head, and the quality of the link between the base station and phone (Gandi and Kang, 2002; Christ et al., 2010). CARCINOGENIC POTENCY OF MW RADIATION In 2011, a group of international experts from IARC (International Agency for Research on Cancer in Lyon) reviewed the available literature on experimental and epidemiologic studies of non thermal RF/MW exposures and concluded that RF/MW radiations should be listed as possible carcinogen (group 2B) for humans (Baan et al., 2011) on the basis of evidence from epidemiologic studies in cell phone users (Baan, 2012). This means that there is some evidence linking mobile phones to cancer, but it is too weak to make any strong conclusions. Specifically, IARCs panel said that the evidence that mobile phones pose a health risk was limited for two types of brain tumors: glioma and neuroma. The 2B category is used for agents, mixtures, and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. The 2B classification of RF/MWs gave rise to controversies among the bioelectromagnetic community, as only a limited number of studies have shown some evidence of statistical association of cell phone use and brain tumor risks, but most studies have found no association. OCCUPATIONAL EXPOSURE TO MWS AND CANCER Reports exist that claim that intense prolonged occupational exposure to MWs may increase risks for cancer. Actually, Robinette et al. (1980) did not find excess mortality in 20,000 U.S. Korean War Naval Veterans 1954 1958 exposed to radar. However, when Groves et al. (2002) conducted a follow-up study of Robinettes cohort, their data did again not find excess cancer, except in one high-exposure occupation group out of three, in which non lymphocytic leukemia was significantly elevated. Recently, Stein et al. (2011) presented a sentinel case series of 47 cancer patients, with occupational exposures to RF/MW radiation. Richter et al. (2000, 2002) reported exposures in a cluster of radar technicians with brain cancer and latent
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Cancer risks of cell phone use

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periods below ten years. Szmigielski (1996) collected retrospective data on all Polish military career personnel exposed to RF/MW during a 15-year period. Cancer rates were analyzed by age groups and higher morbidity rates in the alimentary tract, brain tumors and malignancies of the haematopoietic system and lymphatic organs were noted. The analysis was extended by additional data on military personnel exposed to radar for a period of 20 years (Szmigielski et al., 2001). More recently, Degrave et al. (2005, 2009), in a retrospective cohort study in Belgian male military personnel exposed to anti-aircraft radars in Western Europe between 1960 1990s, found excess incidence of hemolymphatic cancers. These reports indicated that risks for hematolymphatic and brain cancers could be associated with exposures to RF/MWs from radars. Analysis of results reported in all of the above studies strongly suggest that a measurable increase of cancer morbidity occurs in workers with multiyear exposure to relatively strong (but still below thermal levels) MW fields with a latency period of few to several years. The IARC Working Group (Baar et al., 2011) noted, however, that these studies had methodological limitations and the results were inconsistent. In reviewing studies that addressed the possible association between occcupational exposures to RF/MW and cancer, the available evidence was qualified as insufficient for valid conclusion. USE OF CELL PHONES AND CANCER Numerous articles on possible cancer risks in cell phone users have been published in the last decade with controversial results (Vargo et al., 2012). The majority are case-control studies comparing people who already have cancer (cases) with healthy people (controls) and ask them about how they used their phones in the past. Three meta-analyses of case-control studies published before 2007 concluded that using a cell phone for more than ten years was associated with an increase in the overall risk of developing a brain tumor (Kan et al., 2008; Khurana et al., 2009; Myung et al., 2009). All three found statistically significant brain tumors in people who had used a cell phone for more than ten years and one study reported a doubling of glioma on the same (ipsilateral) side the cell phone was used. Early case-control studies were unable to demonstrate a relationship between cell phone use and glioma or meningioma (Johansen et al., 2001; Muscat et al., 2000). In contrast, the Hardells groups case control studies have consistently found associations between brain cancer of all kinds and prior prolonged use of cell phones on the side of the head with the tumor (Hardell et al., 2011). Increase risk for users with over ten years of usage, regardless of age, was reported. However, another large, case-control study in Sweden did not find an increased risk of brain cancer (Lonn et al., 2005). Hardell et al. (2011) did a pooled analysis of two very similar studies of associations between mobile and cordless phone use and glioma, acoustic neuroma, and meningioma. The analysis included 1148 glioma cases (ascertained 1997 2003) and 2438 controls, obtained through cancer and population registries, respectively. Self-administered mailed questionnaires were followed by telephone interviews to obtain information on the exposures and covariates of interest, including use of mobile and cordless phones. Participants who had used a mobile phone for more than 1 year had an OR for glioma of 1.3 (95% CI 1.1 1.6). The OR increased with increasing time since first use and with total call time, reaching 3.2 (2.0 5.1) for more than 2000 h of use. ipsilateral use of the mobile phone was associated with higher risk. Similar findings were reported for use of cordless phones. A cohort study in Denmark linked billing information from more than 420,000 cell phone subscribers with brain tumor incidence data from the Danish Cancer Registry.
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S. Szmigielski

The analyses found no association between cell phone use and the incidence of glioma, meningioma, or acoustic neuroma, even among people who had been cell phone subscribers for 10 or more years (Schuez et al., 2006; Frei et al., 2011). The largest health-related case-control study of the use of cell phones and head and neck tumors is the Interphone Study (2010), conducted by a consortium of researchers from 13 countries. Most published analyses from this study have shown no statistically significant increases in brain or central nervous system cancers related to higher amounts of cell phone use, but they too have found excess risk in a small subgroup of more heavily exposed users associated with latency and laterality (Cardis et al., 2007, 2010). Some subgroups of the Interphone study (Cardis et al., 2010, 2011) found similar data, but some chose to interpret these findings in a subgroup as inconsequential. Morgan (2009) and Vargo (2012) called attention to many methodologic problems with the Interphone study pertaining to selection biases and exposure misclassification. However, one recent analysis showed a statistically significant increase in the risk of glioma among the small proportion of study participants who spent the most total time on cell phone calls (Hardell et al., 2009). Cardis and Sadetzki (2011) published an article in which they endorsed precautionary measures and called attention to potential effects on Public Health from even a small risk at the individual level in over 4 billion people, including children, using cell phones today. They also acknowledged that the Interphone study (2010), like other studies which did not find excess risk, was conducted at a time when mobile communication was still a relatively new phenomenon with low levels of use compared with those of today. Chinese researchers in Beijing (Duan et al., 2011) reported the highest rates of cancer ever reported in any cell phone study. They found that long-term, heavy users have rates of malignant parotid gland tumors that are 7 13 times higher than might otherwise be expected. A number of aspects of the Chinese article do not fit the current understanding of cell phone tumor risks. For instance, Duan et al. (2011) did not see a significant association between the location of the tumor and the preferred side for using a cell phone (known as laterality). In addition, the Chinese team was unable to look at the possible different effects of digital and analog phones, because, they explain, most regular users did not know their cellular phone type. The authors concluded that they cannot exclude the possibility of distortions due to recall or selection bias. They suggested that additional large-scale studies, especially those with a prospective design, be performed to reduce the sources of bias and to confirm the significance of the present results. In addition, the international CEFALO study, which compared children who were diagnosed with brain cancer between the ages of 7 and 19 with similar children who were not, found no relationship between their cell phone use and risk for brain cancer (Aydin et al., 2011). In summary, a limited number of studies have shown some evidence of statistical association of cell phone use and brain tumor risks, but most studies have found no association. Reasons for these discrepancies include schedule of retrospective epidemiologic studies, invalid assessment of MW exposures, based on assessment of dose (period of phone use and cumulative time of calls), or billing (Morgan, 2009). Recall bias, which may happen when a study collects data about prior habits and exposures using questionnaires administered after disease, inaccurate reporting, which may happen when people say that something has happened more or less often than it actually did, and/or participation bias, which can happen when people who are diagnosed with brain tumors are more likely than healthy people to enroll in a research study are discussed as the main reasons for the possible underestimation of cancer risks in multiyear cell phone use. To obtain progress in valid assessment of
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Cancer risks of cell phone use

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cancer risks related to use of cell phones, prospective studies are required. A large prospective cohort study of cell phone use and its possible long-term health effects was launched in the U.K. in March 2010. This study, known as COSMOS (www.ukcosmos.org/index.html), will enroll approximately 250,000 cell phone users ages 18 or older and will follow them for 20 30 years. Participants in COSMOS will complete a questionnaire about their health, lifestyle, and current and past cell phone use. This information will be supplemented with information from health records and cell phone records. Another case-control study, called MobiKids (www.mbkds.net), is underway to examine health effects among children. The challenge of such ambitious studies is to maintain the completeness of their cohorts over many decades. Researchers will need to determine whether participants who leave are somehow different from those who remain throughout the follow-up period. Another problem which demands attention is whether or not children are more sensitive to MWs and remain at higher cancer risks when using cell phones. In theory, children have the potential to be at greater risk than adults for developing brain cancer from cell phones. Their nervous systems are still developing and are therefore more vulnerable to factors that may cause cancer. Their heads are smaller than those of adults and therefore have a greater proportional exposure to the field of radiofrequency radiation that is emitted by cell phones (Gandhi et al., 2002). Additionally, children have the potential of accumulating more years of cell phone exposure than adults do. So far, the data from clinical studies in children do not support this theory. The first published analysis came from a large casecontrol study called CEFALO, which was conducted in Denmark, Sweden, Norway, and Switzerland (Aydin et al., 2011). The study included children who were diagnosed with brain tumors between 2004 and 2008, when their ages ranged from 7 19. Researchers did not find an association between cell phone use and brain tumor risk in this group of children. However, they noted that their results did not rule out the possibility of a slight increase in brain cancer risk among children who use cell phones, and that data gathered through prospective studies and objective measurements, rather than participant surveys and recollections, will be key in clarifying whether there is an increased risk (Aydin et al., 2011). Public concerns of MW radiation emitted from base stations also exist. Base station exposures are much less likely to affect our health than phones themselves as their emissions are many times weaker and usually well below international guidelines. Elliott (2010), in the largest study of its kind, found no association between risk of childhood cancers and mobile phone base station exposures during pregnancy. The authors conclude that the results should help to place any future reports of cancer clusters near mobile phone base stations in a wider public health context. BIOLOGICAL PLAUSIBILITY OF MW CARCINOGENESIS Could cell phone use cause cancer? This is still an open question. Scientists are confident that tobacco, alcohol, or asbestos can cause cancer because they can explain how these things could induce transformation of cells. These explanations are called biological mechanisms play a vital role in establishing that something causes cancer. So far, no one has been able to provide a good biological mechanism for the link between mobile phones and cancer (Vargo et al., 2012). The how question is an open one. The phones give off MW radiation, but this is not powerful enough to damage our DNA. They mildly heat the body, but again, not enough to pose a health risk.
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This imprecise description of MW-related health risks has initiated searches for biological detectors sensitive enough to measure the weak biological influence of MWs. One of main candidates is the immune system, which is able to react in a measurable way to discrete environmental stimuli. As an important part of homeostatic neuroendocrine-immune network of the organism, the immune system is responsible for efficient defense against infections, regenerative support for injured tissues, and maintenance of immune tolerance toward self or foreign but neutral elements (Deschaux and Kahn, 1995). The role of immune system in development of cancer cells, as well as in modification of course of neoplastic ` diseases is well established (Abes and Teillaud, 2011; Sun et al., 2011). These different reactions of the immune system can be investigated using in vitro or in vivo tests to evaluate possible influences of external stimuli (e.g., drugs or physicochemical factors). Unfortunately, available data on the influence of MWs on the immune system are fragmentary, report on changes of few immune functions, mainly phagocytosis, lymphocyte proliferation, or antibody production, and are frequently controversial or not confirmed by the results of repeated experiments (Black, and Heynick, 2003). Some authors (Stavrulakis, 2003), reported immunosuppressive or immunostimulatory phenomena in animals with long-term exposure to low-level MW fields. In summary, studies of immune reactions in animals exposed to MWs provide controversial results with some articles reporting no measurable response, while in others positive results were obtained. The available bulk of evidence from numerous experimental studies in vivo aimed to assess effects of short-term and prolonged low-level MW exposure on function and status of the immune system clearly indicates that various shifts in number and/or activity of immunocompetent cells are possible. However, the results are incoherent; the same functions of lymphocytes are reported to be weaken or enhanced in single experimets with MW exposures at similar intensities and radiation parameters. There exist premises that in general, short-term exposure to weak MWs may temporary stimulate certain humoral or cellular immune fuctions, while prolonged irradiation inhibits the same functions. Articles exist which report changes in NK cell activity or TNF release in MW-eposed animals, but clinical relevance or relation to carcinogenicity of these findings is doubtful. SUMMARY It is understandable that people are concerned about mobile phones, especially because they are so widely used. But so far, the published studies do not show that mobile phones can increase considerably the risk of cancer. This conclusion is backed up by the lack of a solid biological mechanism, and the fact that brain cancer rates are not going up significantly. However, all of the studies so far have weaknesses, which make it impossible to entirely rule out a risk. Mobile phones are still a new technology and there is little evidence about effects of long-term use. For this reason, bioelectromagnetic experts advise application of a precautionary resources. It is suggested that if adults want to use a cell phone, they can choose to minimize their exposure by keeping calls short and preferably using hand-held kits (Morgan, 2009; U.S. Food and Drug Administration, 2009; Vargo et al., 2012). Additionally, it is advised to discourage children under the age of 16 from making non essential calls as well as also keeping their calls short. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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Cancer risks of cell phone use REFERENCES

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